Cited by 201Cell death mechanisms and regulationCancer-related Molecular PathwaysNF-κB Signaling Pathways

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)- Mediated Apoptosis in Human Cancer Cells

Cummins, Jordan M., Kohli, Manu, Rago, Carlo, Kinzler, Kenneth W., Vogelstein, Bert, Bunz, Fred·2004·Cancer Research

Open this paper in CoChat — free account

Abstract

Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-04-0046

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

IAP family proteins---suppressors of apoptosisPreprint
Deveraux, Q. L., & Reed, J. C. (1999) · Genes & Development · doi:10.1101/gad.13.3.239 · Cited by 2,535
Apoptotic Pathways
Green, D. R. (2000) · Cell · doi:10.1016/s0092-8674(00)00003-9 · Cited by 1,011
The inhibitors of apoptosis (IAPs) and their emerging role in cancer
LaCasse, E. C., Baird, S. D., Korneluk, R. G., & MacKenzie, A. (1998) · Oncogene · doi:10.1038/sj.onc.1202569 · Cited by 980
TRAIL and apoptosis induction by TNF-family death receptors
Wang, S., & El‐Deiry, W. S. (2003) · Oncogene · doi:10.1038/sj.onc.1207232 · Cited by 869
Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo
Fulda, S., Wick, W., Weller, M., & Debatin, K. (2002) · Nature Medicine · doi:10.1038/nm735 · Cited by 736
The Drosophila Caspase Inhibitor DIAP1 Is Essential for Cell Survival and Is Negatively Regulated by HID
Wang, S. L., Hawkins, C. J., Yoo, S. J., Müller, H. ‐. J., & Hay, B. A. (1999) · Cell · doi:10.1016/s0092-8674(00)81974-1 · Cited by 517
Characterization of XIAP-Deficient Mice
Harlin, H., Reffey, S. B., Duckett, C. S., Lindsten, T., & Thompson, C. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3604-3608.2001 · Cited by 422
Nature's TRAIL—On a Path to Cancer Immunotherapy
Smyth, M. J., Takeda, K., Hayakawa, Y., Peschon, J. J., van den Brink, M. R. M., & Yagita∥, H. (2003) · Immunity · doi:10.1016/s1074-7613(02)00502-2 · Cited by 360
Targeted transgene insertion into human chromosomes by adeno-associated virus vectors
Hirata, R. K., Chamberlain, J. R., Dong, R., & Russell, D. W. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-735 · Cited by 172
Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative–(BMS 247550) and Apo-2L/TRAIL–induced apoptosis
Guo, F., Nimmanapalli, R., Paranawithana, S. R., Wittmann, S., Griffin, D. R., Bali, P., O’Bryan, E., Fumero, C., Wang, H., & Bhalla, K. N. (2002) · Blood · doi:10.1182/blood.v99.9.3419 · Cited by 162

Show all 14 references

Sorted by citations

Items 101–200 of 201

Expression of anti-apoptotic factors modulates Apo2L/TRAIL resistance in colon carcinoma cells
Lippa, M. S., Strockbine, L. D., Le, T. T., Branstetter, D. G., Strathdee, C. A., & Holland, P. M. (2007) · Apoptosis · doi:10.1007/s10495-007-0076-6 · Cited by 42
“Other reports have also demonstrated that specific targeting of XIAP or FLIP can restore Apo2L/TRAIL sensitivity [26, 41, 53, 54].”
Background
LY303511 amplifies TRAIL-induced apoptosis in tumor cells by enhancing DR5 oligomerization, DISC assembly, and mitochondrial permeabilization
Poh, T. W., Huang, S., Hirpara, J. L., & Pervaiz, S. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402177 · Cited by 42
Mutual regulation between OGT and XIAP to control colon cancer cell growth and invasion
Seo, H. G., Kim, H. B., Yoon, J. Y., Kweon, T. H., Park, Y. S., Kang, J., Jung, J., Son, S., Yi, E. C., Lee, T. H., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02999-5 · Cited by 45
Death receptor expression is associated with poor response to chemotherapy and shorter survival in metastatic ovarian carcinoma
Dong, H. P., Kleinberg, L., Silins, I., Flørenes, V. A., Trope, C. G., Risberg, B. Å., Nesland, J. M., & Davidson, B. (2007) · Cancer · doi:10.1002/cncr.23140 · Cited by 42
Bortezomib Sensitizes Human Esophageal Squamous Cell Carcinoma Cells to TRAIL–Mediated Apoptosis via Activation of Both Extrinsic and Intrinsic Apoptosis Pathways
Seki, N., Toh, U., Sayers, T. J., Fujii, T., Miyagi, M., Akagi, Y., Kusukawa, J., Kage, M., Shirouzu, K., & Yamana, H. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0918 · Cited by 41
Resistance of Cancers to Immunologic Cytotoxicity and Adoptive Immunotherapy via X-Linked Inhibitor of Apoptosis Protein Expression and Coexisting Defects in Mitochondrial Death Signaling
Ravi, R. K., Fuchs, E. J., Jain, A. K., Pham, V., Yoshimura, K., Prouser, T. S., Jalla, S., Zhou, X., Garrett-Mayer, E. S., Kaufmann, S. H., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3377 · Cited by 41
“To determine whether mitochondrial release of Smac is required to counter the inhibition of caspase-3/-7 by endogenous XIAP in tumor cells, we examined the effect of IFN-g and Apo2L/TRAIL on Smac-deficient (Smac / ) or XIAP-deficient (XIAP / ) derivatives of HCT116 cells (35, 36).”
Background
E3 Ligase Activity of XIAP RING Domain Is Required for XIAP-Mediated Cancer Cell Migration, but Not for Its RhoGDI Binding Activity
Liu, J., Zhang, D., Luo, W., Yu, J., Li, J., Yu, Y., Zhang, X., Chen, J., Wu, X., & Huang, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035682 · Cited by 40
“HCT116 cells restored cancer cell motility, whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a role in XIAP regulation of cancer cell motility. Alterations in β-Actin levels…”
Background
Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP
Kim, E. H., Kim, S. U., & Choi, K. S. (2004) · Oncogene · doi:10.1038/sj.onc.1208241 · Cited by 40
Regulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains
Elliott, P. R., Leske, D., Wagstaff, J. L., Schlicher, L., Berridge, G., Maslen, S., Timmermann, F., Ma, B., Fischer, R., Freund, S. M. V., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109777 · Cited by 39
Loss of XIAP sensitizes rosiglitazone‐induced growth inhibition of colon cancer in vivo
Dai, Y., Qiao, L., Chan, K. W., Zou, B., Ma, J., Lan, H. Y., Gu, Q., Li, Z., Wang, Y., Wong, B. L. W., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23443 · Cited by 39
“Human colon cancer cell lines HCT116-XIAP and HCT116-XIAP cells were kind gifts from Professor Bert Vogelstein (Howard Hughes Medical Institute and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, USA).(26) All the primary antibodies except anti-XIAP (MBL International, MA), anti-huma…”
Method
Therapeutic potential of siRNA-mediated combined knockdown of the IAP genes (Livin, XIAP, and Survivin) on human bladder cancer T24 cells
Yang, D., Song, X., Zhang, J., Ye, L., Wang, S., Che, X., Wang, J., Zhang, Z., Wang, L., & Shi, W. (2010) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmp118 · Cited by 37
Smac mimetic reverses resistance to TRAIL and chemotherapy in human urothelial cancer cells
Metwalli, A. R., Khanbolooki, S., Jinesh, G. G., Sundi, D., Shah, J. B., Shrader, M., Choi, W., Lashinger, L. M., Chunduru, S. K., McConkey, D. J., et al. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.9.13237 · Cited by 36
ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells
Yuan, X., Kho, D., Xu, J., Gajan, A., Wu, K., & Wu, G. S. (2017) · Oncotarget · doi:10.18632/oncotarget.15451 · Cited by 36
“Furthermore, some cancer cells, including some types of TNBC, are intrinsically resistant to TRAIL, while others are initially sensitive to TRAIL but later acquire resistance through various mechanisms, including overexpression of members of the anti-apoptotic Bcl-2 family [26-37].”
Background
Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction
Shi, B., Wang, L., Meng, W., Chen, L., & Meng, Z. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.3970 · Cited by 34
Stable XIAP knockdown clones of HCT116 colon cancer cells are more sensitive to TRAIL, taxanes and irradiation in vitro
Connolly, K., Mitter, R., Muir, M., Jodrell, D., & Guichard, S. (2009) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-008-0872-x · Cited by 34
“In colorectal cancer, there is evidence for XIAP as a therapeutic target in vitro in combination with TRAIL [ 36 , 44], in a mouse model of hepatic metastasis in vivo [45] and in clinical samples [29, 46].”
BackgroundMethodResultInfluential
Regulation of the resistance to TRAIL-induced apoptosis in human primary T lymphocytes: Role of NF-κB inhibition
Morales, J. C., Ruiz-Magaña, M. J., & Ruiz‐Ruiz, C. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2006.12.015 · Cited by 34
Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression
Strekalova, E., Malin, D., Rajanala, S. H., & Cryns, V. L. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4201-0 · Cited by 33
“XIAP is a direct inhibitor of caspases that confers resistance to TRAIL-induced caspase-3 activation and apoptosis, while induction of TRAIL-induced apoptosis requires XIAP to be displaced from caspases by mitochondrial release of Smac/ DIABLO [27, 28].”
The Caspase-8 Dimerization/Dissociation Balance Is a Highly Potent Regulator of Caspase-8, -3, -6 Signaling*
Würstle, M. L., Laussmann, M. A., & Rehm, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.113860 · Cited by 33
XIAP promotes melanoma growth by inducing tumour neutrophil infiltration
Daoud, M., Broxtermann, P. N., Schorn, F., Werthenbach, J. P., Seeger, J. M., Schiffmann, L. M., Brinkmann, K., Vucic, D., Tüting, T., Mauch, C., et al. (2022) · EMBO Reports · doi:10.15252/embr.202153608 · Cited by 34
“HCT-XIAP KO cell line was described previously (Cummins et al , 2004).”
IκB Kinase ε-Dependent Phosphorylation and Degradation of X-Linked Inhibitor of Apoptosis Sensitizes Cells to Virus-Induced Apoptosis
Nakhaei, P., Sun, Q., Solis, M., Mésplède, T., Bonneil, É., Paz, S., Lin, R., & Hiscott, J. B. (2011) · Journal of Virology · doi:10.1128/jvi.05989-11 · Cited by 32
“The human colon cancer cell lines HCT116 XIAP / and HCT116 XIAP / , specifically knocked out for XIAP as previously described (12), were cultured in McCoy’s 5A medium.”
Method
Role of GAB1/PI3K/AKT signaling high glucose-induced cardiomyocyte apoptosis
Su, D., Zhou, Y., Hu, S., Guan, L., Shi, C., Wang, Q., Chen, Y., Lu, C., Li, Q., & Ma, X. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.07.063 · Cited by 32
Escaping cell death via TRAIL decoy receptors: a systematic review of their roles and expressions in colorectal cancer
Jong, K. X. J., Mohamed, E. H. M., & Ibrahim, Z. A. (2022) · APOPTOSIS · doi:10.1007/s10495-022-01774-5 · Cited by 30
“A significant number of human cancer progressions have been correlated to the NF-κB activation through the upregulation of several antiapoptotic proteins such as c-IAP2 [47], Bcl-2 [48], XIAP [49] and DcR1 [50].”
Background
Bortezomib sensitises TRAIL-resistant HPV-positive head and neck cancer cells to TRAIL through a caspase-dependent, E6-independent mechanism
Bullenkamp, J., Raulf, N., Ayaz, B., Walczak, H., Kulms, D., Odell, E. W., Thavaraj, S., & Tavassoli, M. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.455 · Cited by 30
“A recent study suggests that TRAIL can exert enhanced cytotoxic activity in cells arrested in G1 or G2 phase.50 Here, bortezomib alone induced clear G2/M arrest in all HPV+ and HPV− HNSCC cell lines, which might contribute to their increased sensitivity to TRAIL.”
BackgroundInfluential
Loss of XIAP sensitizes colon cancer cells to PPARγ independent antitumor effects of troglitazone and 15-PGJ2
Qiao, L., Dai, Y., Gu, Q., Chan, K. W., Ma, J., Lan, H. Y., Zou, B., Röcken, C., Ebert, M. P., & Yu, W. B. C. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.04.003 · Cited by 30
Low expression of XIAP‐associated factor 1 in human colorectal cancers
Tian Le, M. A., Pei Hua, N. I., Zhong, J., Ji Hong, T. A. N., Min Min, Q. I. A. O., & Jiang, S. H. (2005) · Chinese Journal of Digestive Diseases · doi:10.1111/j.1443-9573.2005.00180.x · Cited by 29
Intracellular signaling dynamics during apoptosis execution in the presence or absence of X-linked-inhibitor-of-apoptosis-protein
O'Connor, C. L., Anguissola, S., Huber, H. J., Düßmann, H., Prehn, J. H. M., & Rehm, M. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.05.025 · Cited by 28
“However, in colorectal, breast and pancreatic cancer cells loss of XIAP or reduced XIAP expression was reported to sensitize to TRAIL and CD95-induced apoptosis [17,22,23] and was found to correlate with disturbed lymphocyte homeostasis in humans [24].”
BackgroundMethod
Hispolon from Phellinus linteus induces apoptosis and sensitizes human cancer cells to the tumor necrosis factor-related apoptosis-inducing ligand through upregulation of death receptors
KIM, J.-H., Kim, Y. C., & Park, B. (2015) · Oncology Reports · doi:10.3892/or.2015.4440 · Cited by 27
“These proteins have been linked to suppression of apoptosis by TRAIL, frequently found in TRAIL resistance in a variety of cancer cells including colon (38), breast (39) and kidney cancers (40).”
Background
A dynamical framework for complex fractional killing
Ballweg, R., Paek, A. L., & Zhang, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-07422-2 · Cited by 27
IgG-single-chain TRAIL fusion proteins for tumour therapy
Siegemund, M., Schneider, F., Hutt, M., Seifert, O., Müller, I., Kulms, D., Pfizenmaier, K., & Kontermann, R. E. (2018) · Scientific Reports · doi:10.1038/s41598-018-24450-8 · Cited by 27
HDAC inhibitors with different gene regulation activities depend on the mitochondrial pathway for the sensitization of leukemic T cells to TRAIL-induced apoptosis
Morales, J. C., Ruiz-Magaña, M. J., Carranza, D., Ortiz-Ferrón, G., & Ruiz‐Ruiz, C. (2010) · Cancer Letters · doi:10.1016/j.canlet.2010.04.029 · Cited by 27
“Bcl-xL that impede the activation of the mitochondrial pathway [8]; or the inhibitors of apoptotic proteins XIAP, c-IAP1 and c-IPA2 that inhibit active caspases [9,10].”
Background
Targeting the deubiquitinase STAMBPL1 triggers apoptosis in prostate cancer cells by promoting XIAP degradation
Chen, X., Shi, H., Bi, X., Li, Y., & Huang, Z. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.020 · Cited by 26
Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells
Ouyang, W., Yang, C., Zhang, S., Liu, Y., Yang, B., ZHANG, J., Zhou, F., Zhou, Y., & Xie, C. (2012) · International Journal of Oncology · doi:10.3892/ijo.2012.1748 · Cited by 25
Down-regulation of X-linked inhibitor of apoptosis synergistically enhanced peroxisome proliferator-activated receptor γ ligand-induced growth inhibition in colon cancer
Qiao, L., Dai, Y., Gu, Q., Chan, K. W., Zou, B., Ma, J., Wang, J., Lan, H. Y., & Yu, W. B. C. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0326 · Cited by 25
Hypoxia regulates TRAIL sensitivity of colorectal cancer cells through mitochondrial autophagy
Knoll, G., Bittner, S., Kurz, M., Jantsch, J., & Ehrenschwender, M. (2016) · Oncotarget · doi:10.18632/oncotarget.9206 · Cited by 25
“In line with this hypothesis, XIAP-deficient HCT116 (HCT116 XIAP-/-) cells displayed a tremendously reduced TRAIL resistance under hypoxic conditions (Figure 5A) compared to HCT116 wildtype cells (Figure 1A).”
Method
Parthenolide enhances sensitivity of colorectal cancer cells to TRAIL by inducing death receptor 5 and promotes TRAIL-induced apoptosis
Kim, S., LIU, Y.-C., Park, Y. R., Seo, S. Y., Kim, S., Kim, I. H., Lee, S. O., Lee, S. T., Kim, D.-G., & Kim, S. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2795 · Cited by 24
“TRAIL resistance in CRC cells can occur at several steps in signaling cascade such as deficient receptor redistribution to the membrane, mutation of caspase-8, cellular fas-associated death domain-like interleukin-1-β-converting enzyme-inhibitory protein (cFLIP) expression, Bax deficiency, or through X-linked inhibito…”
Background
β-catenin is regulated by USP9x and mediates resistance to TRAIL-induced apoptosis in breast cancer
Ouyang, W., Zhang, S., Yang, B., Yang, C., ZHANG, J., Zhou, F., & Xie, C. (2015) · Oncology Reports · doi:10.3892/or.2015.4463 · Cited by 24
Signaling through C/EBP Homologous Protein and Death Receptor 5 and Calpain Activation Differentially Regulate THP-1 Cell Maturation-Dependent Apoptosis Induced by Shiga Toxin Type 1
Lee, M., Cherla, R. P., Lentz, E. K., Leyva‐Illades, D., & Tesh, V. L. (2010) · Infection and Immunity · doi:10.1128/iai.00342-10 · Cited by 23
“Furthermore, downregulation of expression of the antiapoptotic Bcl-2 family member Bcl-2 (3, 59), the caspase-8 activation inhibitor c-FLIP (24, 29), or the apoptosis inhibitor XIAP (9) has been shown to sensitize transformed cells to the cytotoxic action of TRAIL.”
Background
Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer
Dai, Y., Qiao, L., Chan, K. W., Yang, M., Ye, J., Zhang, R., Ma, J., Zou, B., Lam, C. S. C., Wang, J., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0509 · Cited by 23
Role of IG20 Splice Variants in TRAIL Resistance
Prabhakar, B. S., Mulherkar, N., & Prasad, K. V. S. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0493 · Cited by 23
Lentivirus-mediated miR-23a overexpression induces trophoblast cell apoptosis through inhibiting X-linked inhibitor of apoptosis
Li, L., Hou, A., Gao, X., Zhang, J., Zhang, L., Wang, J., Li, H., & Song, Y. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.07.082 · Cited by 23
Combinatorial cancer immunotherapy strategies with proapoptotic small-molecule IAP antagonists
Beug, S. T., Conrad, D. P., Alain, T., Korneluk, R. G., & LaCasse, E. C. (2015) · The International Journal of Developmental Biology · doi:10.1387/ijdb.150084el · Cited by 21
MicroRNA-212 inhibits the proliferation, migration and invasion of renal cell carcinoma by targeting X-linked inhibitor of apoptosis protein (XIAP)
Gu, C., Wang, Z., Jin, Z., Li, G., Kou, Y., Jia, Z., Yang, J., & Tian, F. (2017) · Oncotarget · doi:10.18632/oncotarget.20786 · Cited by 21
Heightened JNK Activation and Reduced XIAP Levels Promote TRAIL and Sunitinib-Mediated Apoptosis in Colon Cancer Models
Mahalingam, D., Carew, J. S., Espitia, C. M., Cool, R. H., Giles, F. J., de Jong, S., & Nawrocki, S. T. (2019) · Cancers · doi:10.3390/cancers11070895 · Cited by 22
“Among IAP family members, X-linked inhibitor of apoptosis protein (XIAP) is considered to be the most potent direct inhibitor of caspase activity and has become a strategic target to sensitize cancer cells to apoptosis stimulated by a number of regimens [8,9].”
Background
Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients
Xu, Y., Liu, Q., Dai, J., Yin, Z., Tang, L., Ma, Y., Lin, X., & Wang, H. (2014) · Medical Oncology · doi:10.1007/s12032-013-0764-8 · Cited by 21
“While XIAP does not seem to interfere with basal proliferation of human cancer cells, it does appear to increase sensitivity to tumor necrosis factorrelated apoptosis-inducing ligand and contribute to anoikis resistance [11, 12].”
Background
XIAP is not required for human tumor cell survival in the absence of an exogenous death signal
Sensintaffar, J., Scott, F. L., Peach, R., & Hager, J. H. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-11 · Cited by 21
“Several studies have reported XIAP depletion increases sensitivity to TRAIL mediated apoptosis [10,14,17,23,30-32].”
BackgroundResultInfluential
X-linked inhibitor of apoptosis deficiency in the TRAMP mouse prostate cancer model
Hwang, C., Oetjen, K. A., Kosoff, D., Wojno, K. J., Albertelli, M. A., Dunn, R. L., Robins, D. M., Cooney, K. A., & Duckett, C. S. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.15 · Cited by 21
The pleiotropic profile of the indirubin derivative 6BIO overcomes TRAIL resistance in cancer
Braig, S., Bischoff, F., Abhari, B. A., Meijer, L., Fulda, S., Skaltsounis, A., & Vollmar, A. M. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.07.009 · Cited by 21
“Different studies already used IAP antagonists in combination with chemotherapeutics and death receptor ligands, especially TRAIL, and showed strong synergistic effects on apoptosis induction in several cancer types [45,46].”
Oncogenes as Novel Targets for Cancer Therapy (Part IV)
Zhang, Z., Li, M., Rayburn, E. R., Hill, D. L., Zhang, R., & Wang, H. (2005) · American Journal of PharmacoGenomics · doi:10.2165/00129785-200505060-00006 · Cited by 21
Mathematical Modeling Highlights the Complex Role of AKT in TRAIL-Induced Apoptosis of Colorectal Carcinoma Cells
Anderson, M. W., Moss, J. J., Szalai, R., & Lane, J. D. (2019) · iScience · doi:10.1016/j.isci.2019.01.015 · Cited by 20
The long noncoding RNA XIAP-AS1 promotes XIAP transcription by XIAP-AS1 interacting with Sp1 in gastric cancer cells
Cai, J., Wang, D., Bai, Z., Yin, J., Zhang, J., & Zhang, Z.-T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182433 · Cited by 19
Targeting PP2A inhibits the growth of triple-negative breast cancer cells
Uddin, M. H., Pimentel, J. M., Chatterjee, M., Allen, J. E., Zhuang, Z., & Wu, G. S. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1723195 · Cited by 19
Commitment in apoptosis: slightly dead but mostly alive
Sheridan, C., & Martin, S. J. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.06.002 · Cited by 19
Telomere-Homologous G-Rich Oligonucleotides Sensitize Human Ovarian Cancer Cells to TRAIL-Induced Growth Inhibition and Apoptosis
Sarkar, S., & Faller, D. V. (2013) · Nucleic Acid Therapeutics · doi:10.1089/nat.2012.0401 · Cited by 18
“Other cases of TRAIL resistance are due to increases in FLIP (Hietakangas et al., 2003; ChawlaSarkar et al., 2004; Cummins et al., 2004; Lane et al., 2007; Bae et al., 2008).”
Background
The DeISGylase USP18 limits TRAIL-induced apoptosis through the regulation of TRAIL levels
Manini, I., Sgorbissa, A., Potu, H., Tomasella, A., & Brancolini, C. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.26525 · Cited by 17
Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells
Song, X., Kim, S.-Y., & Lee, Y. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073654 · Cited by 16
“serum [22].”
A Genome-Wide Loss-of-Function Screen Identifies SLC26A2 as a Novel Mediator of TRAIL Resistance
Dimberg, L. Y., Towers, C. G., Behbakht, K., Hotz, T. J., Kim, J., Fosmire, S. P., Porter, C. C., Tan, A. C., Thorburn, A. M., & Ford, H. L. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0234 · Cited by 16
Gene Targeting in Human Somatic Cells
Hendrickson, E. A. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-285-4_53 · Cited by 16
BAY61-3606 potentiates the anti-tumor effects of TRAIL against colon cancer through up-regulating DR4 and down-regulating NF-κB
Du, J., Wang, Y., Chen, D., Ji, G., Ma, Q., Liao, S., Zheng, Y., Zhang, J., & Hou, Y. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.10.002 · Cited by 15
Genomically informed small-molecule drugs overcome resistance to a sustained-release formulation of an engineered death receptor agonist in patient-derived tumor models
Manzari, M. T., Anderson, G. R., Lin, K., Soderquist, R. S., Çakır, M., Zhang, M. Y., Moore, C. E., Skelton, R. N., Fevre, M., Li, X., et al. (2019) · Science Advances · doi:10.1126/sciadv.aaw9162 · Cited by 15
CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45
Dang, L. H., Chen, F., Knock, S. A., Huang, E. H., Feng, J., Appelman, H. D., & Dang, D. T. (2005) · Oncogene · doi:10.1038/sj.onc.1209243 · Cited by 16
“The strategy is as previously described (Chan et al., 2002; Cummins et al., 2004a, b; Kohli et al., 2004; Dang et al., 2005, 2006).”
Method
Parthenolide Sensitizes Human Colorectal Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand through Mitochondrial and Caspase Dependent Pathway
Trang, K. T. T., Kim, S.-L., Park, S.-B., Seo, S.-Y., Choi, C.-H., Park, J.-K., Moon, J.-C., Lee, S.-T., & Kim, S. (2014) · Intestinal Research · doi:10.5217/ir.2014.12.1.34 · Cited by 14
“In colorectal cancer (CRC) cells, several mechanisms contributing to TRAIL resistance have been reported, including deficient receptor redistribution to the membrane,(5) mutation of caspase-8,(6) cellular fas-associated death domain-like interleukin-1-β-converting enzyme-inhibitory protein (cFLIP) expression,(7) Bax d…”
Background
The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats
Zheng, W., Shang, X., Zhang, C., Gao, X., Robinson, B., & Liu, J. (2016) · Cardiology · doi:10.1159/000450825 · Cited by 14
Synthetic ligands of death receptor 5 display a cell-selective agonistic effect at different oligomerization levels
Beyrath, J., Chekkat, N., Smulski, C. R., Lombardo, C. M., Lechner, M., Seguin, C., Décossas, M., Spanedda, M. V., Frisch, B., Guichard, G., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10508 · Cited by 14
“The most studied IAPs, the X-linked inhibitors of apoptosis (XIAP), was for instance shown to mediate TRAIL resistance when overexpressed [39].”
Silencing of X-Linked Inhibitor of Apoptosis Decreases Resistance to Cisplatin and Paclitaxel but Not Gemcitabine in Non-Small Cell Lung Cancer
Liu, Y., Wu, X., Sun, Y., & Chen, F. (2011) · Journal of International Medical Research · doi:10.1177/147323001103900510 · Cited by 12
Inhibitor of apoptosis proteins as E3 ligases for ubiquitin and NEDD8
Kamada, S. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2012-0036 · Cited by 11
Gene expression profile in colon cancer cells with respect to XIAP expression status
Qiao, L., Li, G. H., Dai, Y., Wang, J., Li, Z., Zou, B., Gu, Q., Ma, J., Pang, R. W. C., Lan, H. Y., et al. (2008) · International Journal of Colorectal Disease · doi:10.1007/s00384-008-0566-1 · Cited by 11
“HCT116-XIAP and HCT116-XIAP cells were kind gifts from Professor Bert Vogelstein (Howard Hughes Medical Institute and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, USA) [12].”
BackgroundMethod
Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma
Kang, Z., Sun, S., & Cao, L. (2012) · ISRN Oncology · doi:10.5402/2012/395952 · Cited by 9
“Downstream caspase activity can be further inhibited by XIAP [67] and cIAP [68].”
Background
Antisense approaches in drug discovery and development
Rayburn, E. R., Wang, W., Zhang, R., & Wang, H. (2006) · Birkhäuser-Verlag eBooks · doi:10.1007/3-7643-7414-4_10 · Cited by 8
Dimerization of Smac is crucial for its mitochondrial retention by XIAP subsequent to mitochondrial outer membrane permeabilization
Flanagan, L., Sebastia, J., Delgado, M. E., Lennon, J. C., & Rehm, M. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.02.011 · Cited by 7
“XIAP-deficient DLD-1 and HCT-116 cells and Smacdeficient HCT-116 cells were described before [33,34].”
Background
The Gβ5 protein regulates sensitivity to TRAIL-induced cell death in colon carcinoma
Fuchs, D., Metzig, M. O., Bickeböller, M., Brandel, C., & Roth, W. (2014) · Oncogene · doi:10.1038/onc.2014.213 · Cited by 7
Differential susceptibility of gastric cancer cells to TRAIL-induced apoptosis
SONG, N.-M., Jun, S., Zang, D. Y., Kim, S. G., Park, H., & Kang, D. (2012) · Oncology Reports · doi:10.3892/or.2012.2183 · Cited by 6
“Since XIAP and cellular IAPs (cIAPs) are known to inhibit TRAIL-mediated apoptosis through interaction with caspases, XIAP cleavage may be required to promote TRAIL-mediated cell death (15).”
Influential
Ceramide Analog 5cc Overcomes TRAIL Resistance by Enhancing JNK Activation and Repressing XIAP Expression in Metastatic Colon Cancer Cells
Huang, Q., & Liu, F. (2023) · Chemotherapy · doi:10.1159/000531757 · Cited by 5
“Among the inhibitor of apoptosis protein (IAP) family members, XIAP has been identi ﬁ ed as the most potent direct inhibitor of apoptosis and has become a strategic target for the induction of apoptosis in cancer cells [9, 10].”
Background
A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase
Stagni, V., Santini, S., & Barilà, D. (2012) · Cancers · doi:10.3390/cancers4020354 · Cited by 5
“Genetic targeting of XIAP, as well as IAP antagonists that mimic Smac (an endogenous inhibitor of IAPs), strongly enhances tumor cell sensitivity to TRAIL [44].”
Background
Repeated Recruitment of LTR Retrotransposons as Promoters by the Anti-apoptotic Locus NAIP During Mammalian Evolution
Romanish, M. T., Lock, W. M., van de Lagemaat, L. N., Dunn, C. A., & Mager, D. L. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0030010.eor · Cited by 5
Killing of Kras-Mutant Colon Cancer Cells via Rac-Independent Actin Remodeling by the βGBP Cytokine, a Physiological PI3K Inhibitor Therapeutically Effective In Vivo
Mallucci, L., Shi, D., Davies, D. C., Jordan, P., Nicol, A., Lotti, L. V., Mariani‐Costantini, R., Verginelli, F., Wells, V. E., & Zicha, D. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-1041-t · Cited by 4
“HCT116wt, HCT116mut, DLD1wt and DLD1mut cells, a gift from Bert Vogelstein (John Hopkins University) were cultured as originally reported (28).”
BackgroundMethod
Recent developments in cancer chemotherapy oriented towards new targets
Novotný, L., & Szekeres, T. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.2.343 · Cited by 4
“This means that treatment with TRAIL alone may be insufficient for cancer therapy [89,90].”
Background
Volatile oil of Teucrium alopecurus sensitizes colon cancer cells to TRAIL-induced cell death
Guesmi, F., Prasad, S., Tahri, W., Dridi, I., Ali, M. B., Hedfi, A., Ismail, I. A., & Landoulsi, A. (2021) · Frontiers in Bioscience-Scholar · doi:10.52586/s548 · Cited by 3
“Resistance to TRAIL has been also shown to associated with overexpression of anti-apoptotic proteins XIAP and survivin in colon cancer [51] and their inhibition found to”
Background
Inhibition of MEK sensitizes gastric cancer cells to TRAIL-induced apoptosis
Wu, P., Cheng, Y., WANG, J. Y., Zhang, X. D., & ZHANG, L. J. (2013) · Neoplasma · doi:10.4149/neo_2014_019 · Cited by 3
“In parallel, Smac/ DIABLO leaves intermembrane compartment of mitochondria and releases caspase-3 and caspase-9 from Inhibitor of apoptosis proteins (IAPs) -mediated inhibition [2].”
BackgroundInfluential
CPT21, a novel compound with anti-proliferative effect against gastric cancer cell SGC7901
Zhang, B., Luo, Y., Weng, Q., He, Q., Lu, W. P., & Yang, B. (2008) · Investigational New Drugs · doi:10.1007/s10637-008-9120-9 · Cited by 3
“These proteins act directly on caspases, distal to mitochondrial perturbation [27, 28 ].”
Background
Mechanism of bFGF-binding Peptide Reversing Adriamycin Resistance in Human Gastric Cancer Cells
Tan, X., Chen, X., Huang, T., Luo, W., He, D. N., Lin, X., Li, S., & Wu, X. (2014) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-014-9402-3 · Cited by 2
Therapeutic Modulation of Apoptosis in Cancer Therapy
Fulda, S., & Debatin, K. (2006) · Wiley eBooks · doi:10.1002/9783527619665.ch33 · Cited by 2
Targeting of TRAIL Apoptotic Pathways for Glioblastoma Therapies
Bellail, A. C., Mulligan, P., & Hao, C. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-553-8_41 · Cited by 2
SMAC IAP Addiction in Cancer
Brown, M. F., He, K., & Yu, J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-5847-0_10 · Cited by 1
Human Soluble TRAIL Secreted by Modified Lactococcus lactis Bacteria Promotes Tumor Growth in the Orthotopic Mouse Model of Colorectal Cancer
Kaczmarek, K., Wieckiewicz, J., Que, I., Gałuszka-Bulaga, A., Chan, A. B., Siedlar, M., & Baran, J. (2024) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.2478/aite-2024-0002 · Cited by 1
“For many years TRAIL has been shown to induce apoptosis of sensitive cancer cells, however this sensitivity quite often revealed to be only temporary and was lost in many cancers during the treatment (Hernandez et al., 2001; Galligan et al., 2005; Cummins et al., 2004).”
Role of X-Linked Inhibitor of Apoptosis Protein in Therapeutic Resistance of Inflammatory Breast Cancer Cells
Aird, K. M. (2010) · DukeSpace (Duke University) · Cited by 1
Regulation of cancer cell growth and death: Evaluating new anticancer targets
Bunz, F. (2005) · Drug Discovery Today Disease Mechanisms · doi:10.1016/j.ddmec.2005.08.006 · Cited by 1
Self-citation
Overcoming Cancer Cell Resistance to Death Receptor Targeted Therapies
Twomey, J. D., Hallett, W. H. D., & Zhang, B. (2015) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-17807-3_10
Efficacy and Mechanistic Evaluation of Tic10, A Novel Antitumor Agent
Allen, J. E. (2012) · ScholarlyCommons (University of Pennsylvania)
Estudio de los mecanismos que regulan la expresión y función del ligando de muerte TRAIL en células T normales y leucémicas
Camino, J. C. M. (2011)
Small‐molecule Inhibitors of the Inhibitor of Apoptosis Proteins
Armstrong, R. C., Belli, B., & Deckwerth, T. L. (2006) · doi:10.1002/9783527619665.ch36
Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer
Xu, L. (2006) · Defense Technical Information Center (DTIC)
Implication of TNF superfamily receptors and their functional antagonists in neuronal apoptotic cell death
Gozzelino, R. (2007) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Targeting of the Myc pathway as a novel approach for cancer therapy
Mo, H. (2006) · Figshare
Human Cancer Resistance to Trail-Apoptotic Pathway-Targeted Therapies
Bellail, A. C., & Hao, C. (2013) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-1-4614-7070-0_11
Mathematical Models of Some Signaling Pathways Regulating Cell Survival and Death
Zhang, T., Tyson, J. J., Brazhnik, P., Li, L., Mendes, P., Finkielstein, C. V., & Burns, J. A. (2008) · VTechWorks (Virginia Tech)
MICROARRAYS AND OTHER NEW TECHNOLOGIES Recurrent Genomic Alterations With Impact on Survival in Colorectal Cancer Identified by Genome-Wide Array Comparative Genomic Hybridization
Yim, H., Lee, C., & Chung, Y. (2006)
Supplementary Methods SM2 from A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer
Salvucci, M., Würstle, M. L., Morgan, C., Curry, S., Cremona, M., Lindner, A. U., Bacon, O., Resler, A. J., Murphy, Á. C., O’Byrne, R., et al. (2023) · doi:10.1158/1078-0432.22467299.v1
Supplementary Methods SM2 from A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer
Salvucci, M., Würstle, M. L., Morgan, C., Curry, S., Cremona, M., Lindner, A. U., Bacon, O., Resler, A. J., Murphy, Á. C., O’Byrne, R., et al. (2023) · doi:10.1158/1078-0432.22467299
Résistance à l'apoptose induite par TRAIL-R4 : sensibilisation des cellules tumorales par la chimiothérapie ou des mimétiques de TRAIL
Morizot, A. (2010) · theses.fr (ABES) · doi:10.70675/e51fe6dezdbbcz4b2ez9cdczb2bd85fa0361
The Role of the XIAP Gene in Human Pathology
Shavrak, V. E., & Skryabin, N. A. (2026) · Russian Journal of Genetics · doi:10.1134/s1022795426700286

Authors: Cummins, J. M., Kohli, M., Rago, C., Kinzler, K. W., Vogelstein, B., & Bunz, F.
Affiliations: Johns Hopkins University (US)
Sidney Kimmel Cancer Center (US)
Howard Hughes Medical Institute (US)
ORCID: Kohli, Manu
Kinzler, Kenneth W.
Vogelstein, Bert
Bunz, Fred
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2004-05-01
Volume: 64
Issue: 9
Pages: 3006-3008
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-04-0046
OpenAlex: W2074501845
Cited by: 200
References: 14
Citations by year: 2026: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 10 · 2016: 4 · 2015: 4 · 2014: 16 · 2013: 8 · 2012: 18
FWCI: 6.53
Type: journal article
Language: en
Open access: closed
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA43460)
National Institute of General Medical Sciences (T32GM007309, GM07309)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: XIAP, inhibitor of apoptosis proteins, TRAIL, TRAIL resistance, apoptosis, cancer cells, gene targeting, cancer therapy targets, immune surveillance
MeSH terms: Cell Survival, Colonic Neoplasms, Humans, Membrane Glycoproteins, Proteins, Tumor Necrosis Factor-alpha, Apoptosis, Caspases, HCT116 Cells, Cell Line, Tumor, Apoptosis Regulatory Proteins, X-Linked Inhibitor of Apoptosis Protein, TNF-Related Apoptosis-Inducing Ligand

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)- Mediated Apoptosis in Human Cancer Cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks