Inhibition of isoprenylcysteine carboxylmethyltransferase induces autophagic-dependent apoptosis and impairs tumor growth
Abstract
Inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final step in the post-translational C-terminal processing of prenylated proteins, suppresses tumor cell growth and induces cell death. Icmt inhibition by either a small molecule inhibitor termed as cysmethynil or inhibitory RNA induces marked autophagy leading to cell death. HepG2 cells were used to investigate the function of autophagy in tumor cell death. Suppression of autophagy, either pharmacologically or through knockdown of the autophagy essential proteins, Atg5 or Atg1, inhibits not only cysmethynil-induced autophagy, but also apoptosis in HepG2 cells. The dependence of cysmethynil-induced apoptosis on autophagy was further shown using autophagy-deficient mouse embryonic fibroblast (MEF) cells. Atg5(-/-) MEF cells were found to be resistant to cysmethynil-induced apoptosis, whereas wild-type MEFs showed high sensitivity to apoptosis induction. These data indicate that inhibition of Icmt can elicit cell death through two linked mechanisms, autophagy and apoptosis, and that autophagy can be an active player upstream of apoptosis in cell types capable of apoptotic cell death, such as HepG2 and MEFs. Further, treatment of mice-bearing HepG2-derived tumors with cysmethynil resulted in marked inhibition of tumor growth; analysis of tumor tissue from these mice revealed markers consistent with autophagy induction and cell growth arrest.
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Cysmethynil, a small molecule inhibitor of ICMT, disrupts RAS membrane binding and reduces cell growth in RAS mutant cell lines.
“Cysmethynil, a small molecule inhibitor of ICMT, disrupts RAS membrane binding and reduces cell growth in RAS mutant cell lines [46–48].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [47]
Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Autophagy as a regulated pathway of cellular degradation.
Klionsky, D., & Emr, S. (2000) · Science · doi:10.1126/science.290.5497.1717 · Cited by 3,794 · see citing works
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865 · see citing works
Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116 · see citing works
PROTEIN PRENYLATION: Molecular Mechanisms and Functional Consequences
Zhang, F. L., & Casey, P. J. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.001325 · Cited by 2,018 · see citing works
Self-citationLC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation
Kabeya, Y., Mizushima, N., Yamamoto, A., Oshitani-Okamoto, S., Ohsumi, Y., & Yoshimori, T. (2004) · Journal of Cell Science · doi:10.1242/jcs.01131 · Cited by 1,394 · see citing works
DRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P. R., Gasco, M., Garrone, O., Crook, T., & Ryan, K. M. (2006) · Cell · doi:10.1016/j.cell.2006.05.034 · Cited by 1,380 · see citing works
Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis
Yousefi, S., Perozzo, R., Schmid, I., Ziemiecki, A., Schaffner, T. J., Scapozza, L., Brunner, T., & Simon, H. (2006) · Nature Cell Biology · doi:10.1038/ncb1482 · Cited by 1,300 · see citing works
Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells
Kanzawa, T., Germano, I. M., Komata, T., Ito, H., Kondo, Y., & Kondo, S. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401359 · Cited by 986 · see citing works
Lockshin, R. A., & Beaulaton, J. (1974) · Life Sciences · doi:10.1016/0024-3205(74)90321-x · Cited by 955 · see citing works
K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors
Whyte, D. B., Kirschmeier, P., Hockenberry, T. N., Nunez-Oliva, I., James, L., Catino, J. J., Bishop, W. R., & Pai, J.-K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14459 · Cited by 884 · see citing works
Direct Induction of Autophagy by Atg1 Inhibits Cell Growth and Induces Apoptotic Cell Death
Scott, R. C., Juhász, G., & Neufeld, T. P. (2007) · Current Biology · doi:10.1016/j.cub.2006.10.053 · Cited by 852 · see citing works
Takeuchi, H., Kondo, Y., Fujiwara, K., Kanzawa, T., Aoki, H., Mills, G. B., & Kondo, S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3640 · Cited by 534 · see citing works
Do all programmed cell deaths occur via apoptosis?
Schwartz, L. M., Smith, S. W., Jones, M. E. E., & Osborne, B. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.3.980 · Cited by 533 · see citing works
NF-κB Activation Represses Tumor Necrosis Factor-α-induced Autophagy
Djavaheri‐Mergny, M., Amelotti, M., Mathieu, J., Besançon, F., Bauvy, C., Souquère, S., Pierron, G., & Codogno, P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602097200 · Cited by 467 · see citing works
Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4
Espert, L. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26185 · Cited by 447 · see citing works
Post-prenylation-processing enzymes as new targets in oncogenesis
Winter-Vann, A. M., & Casey, P. J. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1612 · Cited by 357 · see citing works
Self-citationHuang, J., & Klionsky, D. J. (2007) · Cell Cycle · doi:10.4161/cc.6.15.4511 · Cited by 316 · see citing works
Programmed Cell Death (PCD): Apoptosis, Autophagic PCD, or Others?
Bursch, W., Ellinger, A., Gerner, C., Fröhwein, U., & Schulte‐Hermann, R. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05594.x · Cited by 311 · see citing works
Mammalian Prenylcysteine Carboxyl Methyltransferase Is in the Endoplasmic Reticulum
Dai, Q., Choy, E., Chiu, V. K., Romano, J. D., Slivka, S. R., Steitz, S. A., Michaelis, S., & Philips, M. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.24.15030 · Cited by 296 · see citing works
Dual roles of autophagy in the survival of <i>Caenorhabditis elegans</i> during starvation
Kang, C., You, Y.-J., & Avery, L. (2007) · Genes & Development · doi:10.1101/gad.1573107 · Cited by 294 · cited 2× · see citing works
“Autophagy exists in all eukaryotic cells, having apparently evolved as a tightly regulated mechanism to cope with a nutrient-deficient environment (Kuma et al., 2004; Kang et al., 2007).”
BackgroundMethodDoes autophagy have a license to kill mammalian cells?
Scarlatti, F., Granata, R., Meijer, A., & Codogno, P. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2008.101 · Cited by 271 · see citing works
Akar, U., Chaves-Reyez, A., Barria, M., Tari, A. M., Sanguino, A. M., Kondo, Y., Kondo, S., Arun, B. K., Lopez‐Berestein, G., & Özpolat, B. (2008) · Autophagy · doi:10.4161/auto.6083 · Cited by 253 · see citing works
Futreal, P. A., Söderkvist, P., Marks, J. R., Iglehart, J. D., Cochran, C., Barrett, J. C., & Wiseman, R. W. (1992) · PubMed · Cited by 200 · see citing works
Therapeutic intervention based on protein prenylation and associated modifications
Gelb, M. H., Brunsveld, L., Hrycyna, C. A., Michaelis, S., Tamanoi, F., Voorhis, W. C. V., & Waldmann, H. (2006) · Nature Chemical Biology · doi:10.1038/nchembio818 · Cited by 195 · see citing works
Saito, H., Inazawa, J., Saito, H., Kasumi, F., Koi, S., Sagae, S., Kudo, R., Saito, J., Noda, K., & Nakamura, Y. (1993) · PubMed · Cited by 192 · see citing works
Autophagy in aging, disease and death: the true identity of a cell death impostor
Levine, B., & Kroemer, G. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.139 · Cited by 180 · see citing works
Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf
Bergö, M. O., Gavino, B. J., Hong, C., Beigneux, A. P., McMahon, M., Casey, P. J., & Young, S. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci18829 · Cited by 180 · see citing works
Self-citationInactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf
Bergo, M. O., Gavino, B. J., Hong, C., Beigneux, A. P., McMahon, M., Casey, P. J., & Young, S. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200418829 · Cited by 180 · see citing works
Self-citationWinter-Vann, A. M., Baron, R. A., Wong, W., dela Cruz, J., York, J. D., Gooden, D. M., Bergo, M. O., Young, S. G., Toone, E. J., & Casey, P. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408107102 · Cited by 178 · see citing works
Self-citationMolecular Mechanisms and Regulation of Specific and Nonspecific Autophagy Pathways in Yeast*
Nair, U., & Klionsky, D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.r500016200 · Cited by 155 · see citing works
Autophagy Signaling and the Cogwheels of Cancer
Botti, J., Djavaheri‐Mergny, M., Pilatte, Y., & Codogno, P. (2006) · Autophagy · doi:10.4161/auto.2.2.2458 · Cited by 153 · see citing works
Farnesyltransferase Inhibitors: A Detailed Chemical View on an Elusive Biological Problem
Sousa, S. F., Fernandes, P. A., & Ramos, M. J. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708784638825 · Cited by 121 · see citing works
Wang, M., Tan, W., Zhou, J., Leow, J., Go, M., Lee, H. S., & Casey, P. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801855200 · Cited by 115 · see citing works
Self-citationLambert, L., Qiao, N., Hunt, K. K., Lambert, D. H., Mills, G. B., Meijer, L., & Keyomarsi, K. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1333 · Cited by 113 · see citing works
Fatty acylation and prenylation of proteins: what's hot in fat
Magee, T., & Seabra, M. C. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.02.003 · Cited by 112 · see citing works
Apparent caspase independence of programmed cell death in Dictyostelium
Olie, R. A., Durrieu, F., Cornillon, S., Loughran, G., Gross, J. D., Earnshaw, W. C., & Golstein, P. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70395-1 · Cited by 108 · see citing works
Redistribution of U-snRNPs during mitosis
Spector, D. L., & Smith, H. C. (1986) · Experimental Cell Research · doi:10.1016/0014-4827(86)90560-4 · Cited by 106 · see citing works
The Drosophila homolog of Aut1 is essential for autophagy and development
Juhász, G., Csikós, G., Sinka, R., Erdélyi, M., & Sass, M. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00431-9 · Cited by 105 · see citing works
Inactivating Icmt ameliorates K-RAS–induced myeloproliferative disease
Wahlstrom, A. M., Cutts, B. A., Liu, M., Lindskog, A., Karlsson, C., Sjogren, A.-K. M., Andersson, K., Young, S. G., & Bergö, M. O. (2008) · Blood · doi:10.1182/blood-2007-06-094060 · Cited by 92 · see citing works
Ashby, M. N. (1998) · Current Opinion in Lipidology · doi:10.1097/00041433-199804000-00004 · Cited by 85 · see citing works
Promotion of autophagy as a mechanism for radiation sensitization of breast tumor cells
Gewirtz, D. A., Bristol, M. L., & Wilson, E. N. (2009) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2009.05.022 · Cited by 84 · see citing works
Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group.
Eccles, D., Russell, S. E. H., Haites, N. E., Atkinson, R., Bell, D. W., Gruber, L., Hickey, I., Kelly, K., Kitchener, H. C., & Leonard, R. C. (1992) · PubMed · Cited by 84 · see citing works
Di, X. M., Shiu, R. P. C., Newsham, I., & Gewirtz, D. A. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.12.016 · Cited by 76 · see citing works
Developmental Cell Death in Dictyostelium Does Not Require Paracaspase
Roisin-Bouffay, C., Luciani, M., Klein, G., Levraud, J., Adam, M., & Golstein, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312741200 · Cited by 75 · see citing works
Inhibitors of Chronically Active Ras: Potential for Treatment of Human Malignancies
Kloog, Y., Blum, R., & Cox, A. D. (2008) · Recent Patents on Anti-Cancer Drug Discovery · doi:10.2174/157489208783478702 · Cited by 64 · see citing works
Isoprenylcysteine Carboxyl Methyltransferase Activity Modulates Endothelial Cell Apoptosis
Kramer, K., Harrington, E. O., Lü, Q., Bellas, R. E., Newton, J., Sheahan, K. L., & Rounds, S. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-07-0390 · Cited by 55 · see citing works
Górka, M., Daniewski, W. M., Gajkowska, B., Łusakowska, E., Godlewski, M. M., & Motyl, T. (2005) · Anti-Cancer Drugs · doi:10.1097/01.cad.0000171514.50310.85 · Cited by 38 · see citing works
The Isoprenoid Substrate Specificity of Isoprenylcysteine Carboxylmethyltransferase
Anderson, J. L., Henriksen, B. S., Gibbs, R. A., & Hrycyna, C. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504982200 · Cited by 38 · see citing works
Wright, L. P., Court, H., Mor, A., Ahearn, I. M., Casey, P. J., & Philips, M. R. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01719-08 · Cited by 31 · see citing works
Self-citationBaron, R., Peterson, Y. K., Otto, J. C., Rudolph, J., & Casey, P. J. (2006) · Biochemistry · doi:10.1021/bi060344n · Cited by 22 · see citing works
Self-citationAbsence of Prohibitin Gene Mutations in Human Epithelial Ovarian Tumors
Cliby, W. A., Sarkar, G., Ritland, S. R., Hartmann, L. C., Podratz, K. C., & Jenkins, R. B. (1993) · Gynecologic Oncology · doi:10.1006/gyno.1993.1160 · Cited by 17 · see citing works
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Targeting protein prenylation for cancer therapy
Berndt, N., Hamilton, A. D., & Sebti, S. M. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3151 · Cited by 614 · see citing works
Protein prenylation: unique fats make their mark on biology
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Self-citationTherapeutic Strategies for Targeting Ras Proteins
Gysin, S., Salt, M. B., Young, A. E., & McCormick, F. (2011) · Genes & Cancer · doi:10.1177/1947601911412376 · Cited by 321 · see citing works
Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Zhu, C., Guan, X., Zhang, X., Luan, X., Song, Z., Cheng, X., Zhang, W., & Qin, J.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01629-2 · Cited by 231 · see citing works
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Ward, A. F., Braun, B. S., & Shannon, K. (2012) · Blood · doi:10.1182/blood-2012-05-378596 · Cited by 207 · see citing works
Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer
El‐Khattouti, A., Selimović, D., Haïkel, Y., & Hassan, M. (2013) · Journal of Cell Death · doi:10.4137/jcd.s11034 · Cited by 121 · see citing works
Ras and autophagy in cancer development and therapy
Schmukler, E., Kloog, Y., & Pinkas‐Kramarski, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1775 · Cited by 108 · see citing works
Yuan, Y., Li, P., Li, J., Zhao, Q., Chang, Y., & He, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01759-7 · Cited by 112 · see citing works
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Tiwari, M., Sharma, L. K., Vanegas, D., Callaway, D. A., Bai, Y., Lechleiter, J. D., & Herman, B. A. (2014) · Autophagy · doi:10.4161/auto.28528 · Cited by 75 · see citing works
Lau, H. Y., Ramanujulu, P. M., Guo, D., Yang, T., Wirawan, M., Casey, P. J., Go, M., & Wang, M. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.29692 · Cited by 62 · see citing works
Self-citationBisphosphonates Induce Autophagy by Depleting Geranylgeranyl Diphosphate
Wasko, B. M., Dudakovic, A., & Hohl, R. J. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.175521 · Cited by 62 · see citing works
Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets
Tate, E. W., Soday, L., de la Lastra, A. L., Wang, M., & Lin, H. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00666-x · Cited by 61 · see citing works
Self-citationIn vitro toxicological assessment of clays for their use in food packaging applications
Maisanaba, S., Puerto, M., Pichardo, S., Jordá-Beneyto, M., Moreno, F. J., Aucejo, S., & Jos, A. M. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.03.043 · Cited by 59 · see citing works
Yang, J., Kulkarni, K. A., Manolaridis, I., Zhang, Z., Dodd, R. B., Mas-Droux, C., & Barford, D. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.10.020 · Cited by 57 · see citing works
Manu, K. A., Chai, T. F., Teh, J. T., Zhu, W. L., Casey, P. J., & Wang, M. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0703 · Cited by 55 · see citing works
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Negri, F., Bottarelli, L., de’Angelis, G. L., & Gnetti, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084120 · Cited by 55 · see citing works
Zverina, E. A., Lamphear, C. L., Wright, E. N., & Fierke, C. A. (2012) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.10.015 · Cited by 51 · see citing works
Zhou, H., Fang, J., Luo, X., Zhang, L., Yang, J., Zhang, C., & Zhuang, S. (2014) · Oncotarget · doi:10.18632/oncotarget.2601 · Cited by 49 · see citing works
Garant, K. A., Shmulevitz, M., Pan, L., Daigle, R., Ahn, D.-G., Gujar, S. A., & Lee, P. W. K. (2015) · Oncogene · doi:10.1038/onc.2015.136 · Cited by 47 · see citing works
Kim, J. H., Kim, J. H., Kim, S. C., Yi, Y., Yang, W. S., Yang, Y., Kim, H. G., Lee, J. Y., Kim, K., Yoo, B. C., et al. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.08.022 · Cited by 48 · see citing works
Marín‐Ramos, N. I., Balabasquer, M., Ortega-Nogales, F. J., Torrecillas, I. R., Gil-Ordóñez, A., Marcos‐Ramiro, B., Aguilar-Garrido, P., Cushman, I., Romero, A., Medrano, F. J., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00145 · Cited by 49 · see citing works
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Manu, K. A., Cao, P. H. A., Chai, T. F., Casey, P. J., & Wang, M. (2019) · Cancers · doi:10.3390/cancers11081112 · Cited by 47 · see citing works
Self-citationLau, H. Y., Tang, J., Casey, P. J., & Wang, M. (2017) · Oncogene · doi:10.1038/onc.2016.508 · Cited by 46 · see citing works
Self-citationResearch progress on KRAS mutations in colorectal cancer
Cefalì, M., Epistolio, S., Palmarocchi, M. C., Frattini, M., & Dosso, S. D. (2021) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2021.61 · Cited by 47 · see citing works
Targeting the RAS upstream and downstream signaling pathway for cancer treatment
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Self-citationZhao, Y., Fan, D., Ru, B., Cheng, K., Hu, S., Zhang, J., Li, E. T. S., & Wang, M. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.09.001 · Cited by 43 · see citing works
Self-citationA Role for Rac3 GTPase in the Regulation of Autophagy
Zhu, W., Hossain, M. S., Guo, D. Y., Liu, S., Tong, H., Khakpoor, A., Casey, P. J., & Wang, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.280990 · Cited by 36 · see citing works
Self-citationDo, M. T., Chai, T. F., Casey, P. J., & Wang, M. (2017) · Oncogene · doi:10.1038/onc.2017.183 · Cited by 35 · see citing works
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Pandey, D., Chauhan, S. C., Kashyap, V. K., & Roy, K. K. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116771 · Cited by 32 · see citing works
Teh, J. T., Zhu, W., Ilkayeva, O., Li, Y., Gooding, J. R., Casey, P. J., Summers, S. A., Newgard, C. B., & Wang, M. (2014) · Oncogene · doi:10.1038/onc.2014.260 · Cited by 31 · see citing works
Self-citationZhao, M., Chen, Q., Xu, W., Wang, H., Che, Y., Wu, M., Wang, L., Lijuan, C., & Hao, H. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112093 · Cited by 29 · see citing works
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Weidle, U. H., SCHMID, D., Birzele, F., & Brinkmann, U. (2019) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20163 · Cited by 28 · see citing works
Ramanujulu, P. M., Yang, T., Yap, S.-Q., Wong, F. M., Casey, P. J., Wang, M., & Go, M. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.02.007 · Cited by 28 · see citing works
Self-citationZhu, W., Tong, H., Teh, J. T., & Wang, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115087 · Cited by 25 · see citing works
Self-citationBhadoriya, K. S., Sharma, M. C., & Jain, S. V. (2014) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2014.10.036 · Cited by 24 · see citing works
Sun, X., & Yan, H. (2021) · Journal of International Medical Research · doi:10.1177/0300060520939031 · Cited by 21 · see citing works
Chai, T. F., Manu, K. A., Casey, P. J., & Wang, M. (2020) · Oncogene · doi:10.1038/s41388-020-1364-7 · Cited by 20 · see citing works
Self-citationPan, Q., Liu, R., Banu, H., Ma, L., & Li, H. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.01.048 · Cited by 20 · see citing works
Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics
Xu, M., & Xu, B. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02309-7 · Cited by 18 · see citing works
Xu, J., Zhu, Y., Wang, F., Zhou, Y., Xia, G., & Xu, W. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.08.094 · Cited by 18 · see citing works
Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene
Haidar, M., & Jacquemin, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413193 · Cited by 16 · see citing works
Tamanoi, F., & Lu, J. (2013) · The Enzymes · doi:10.1016/b978-0-12-420146-0.00008-1 · Cited by 17 · see citing works
Diver, M. M., & Long, S. B. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.585125 · Cited by 15 · see citing works
Hsu, C., Faisal, A., Jumaa, S. S., Gilmanova, N. S., Ubaid, M., Athab, A. H., Mirzaei, R., & Karampoor, S. (2024) · Non-coding RNA Research · doi:10.1016/j.ncrna.2024.05.001 · Cited by 14 · see citing works
Deconvoluting the biology and druggability of protein lipidation using chemical proteomics
de la Lastra, A. L., Hassan, S., & Tate, E. W. (2020) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2020.10.002 · Cited by 14 · see citing works
Regulation of autophagy by protein lipidation
Shao, Y., Hu, J., Li, H., & Lu, K. (2024) · Advanced Biotechnology · doi:10.1007/s44307-024-00040-w · Cited by 13 · see citing works
The Emerging Role of p21 in Diabetes and Related Metabolic Disorders
ElMitwalli, O. S., Darwish, R., Al-Jabery, L., Algahiny, A. T., Roy, S., Butler, A. E., & Hasan, A. S. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313209 · Cited by 17 · see citing works
Li, Y., Gao, X., Yang, C., Yan, H., & Li, C. (2022) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24348 · Cited by 13 · see citing works
Liu, Q., Chen, J., Fu, B., Dai, J., Zhao, Y., & Lai, L. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.038 · Cited by 12 · see citing works
RAB4A is a master regulator of cancer cell stemness upstream of NUMB–NOTCH signaling
Karthikeyan, S., Casey, P. J., & Wang, M. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07172-w · Cited by 11 · see citing works
Self-citationMagkouta, S., Pappas, A., Moschos, C., Vazakidou, M., Psarra, K., & Kalomenidis, I. (2016) · Oncotarget · doi:10.18632/oncotarget.7912 · Cited by 11 · see citing works
Sun, W. T., Xiang, W., Ng, B. L., Asari, K., Bunte, R. M., Casey, P. J., Wang, M., & Chuah, C. T. H. (2015) · Experimental Hematology · doi:10.1016/j.exphem.2015.12.002 · Cited by 11 · see citing works
Self-citationHuang, J., Yang, X., Peng, X., & Huang, W. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.09.120 · Cited by 10 · see citing works
Zhu, Y., Hu, Q., & Li, H. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.06.074 · Cited by 9 · see citing works
Lau, H. Y., Tang, J., Casey, P. J., & Wang, M. (2021) · Cancers · doi:10.3390/cancers13040807 · Cited by 9 · see citing works
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Arendt, K. A. M., Ntaliarda, G., Armenis, V., Kati, D., Henning, C., Giotopoulou, G. A., Pepe, M. A. A., Klotz, L. V., Lamort, A., Hatz, R. A., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10030592 · Cited by 7 · see citing works
RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation
Karthikeyan, S., Casey, P. J., & Wang, M. (2022) · Breast Cancer Research · doi:10.1186/s13058-022-01564-6 · Cited by 7 · see citing works
Self-citationActivation of Ras by Post-Translational Modifications
Xiang, S., Bai, W., Bepler, G., & Zhang, X. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803505-4.00006-0 · Cited by 7 · see citing works
Lau, H. Y., & Wang, M. (2017) · Small GTPases · doi:10.1080/21541248.2017.1415637 · Cited by 7 · see citing works
Self-citationThe role of ral signaling and post translational modifications (PTMs) of Ras in cancer
Zinatizadeh, M. R., Zarandi, P. K., Keshavarz‐Fathi, M., Yousefi, M. H., & Rezaei, N. (2022) · Genome Instability & Disease · doi:10.1007/s42764-022-00059-0 · Cited by 6 · see citing works
The interplay between Ras, Autophagy and cancer
Schmukler, E., & Pinkas‐Kramarski, R. (2021) · Advances in Cancer Biology - Metastasis · doi:10.1016/j.adcanc.2021.100014 · Cited by 5 · see citing works
Wang, S., Wang, W. T., Zhang, S., Yang, F., Qiu, J. Y., Guo, Q., Zheng, J., & Chen, Z. (2021) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2021.105320 · Cited by 3 · see citing works
Novel bisphosphonates as inhibitors of isoprenoid biosynthesis
Wasko, B. M. (2011) · doi:10.17077/etd.zcat0wc9 · Cited by 3 · see citing works
Mechanisms of CaaX Protein Processing: Protein Prenylation by FTase and GGTase-I
Blanden, M. J., Ashok, S., & Hougland, J. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14837-1 · Cited by 2 · see citing works
Wang, S., Sun, W., Zhou, N., Zhao, K., Li, W., Chi, Z.-P., Wang, Y., Wang, Q., Tong, L., He, Z., et al. (2021) · PubMed Central · doi:10.7518/hxkq.2021.01.010 · Cited by 1 · see citing works
Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair
Tang, J., Casey, P. J., & Wang, M. (2021) · Life Science Alliance · doi:10.26508/lsa.202101144 · Cited by 1 · see citing works
Self-citationSearch for Inhibitors of Ras-Driven Cancers
Keeton, A. B., & Piazza, G. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803505-4.00008-4 · Cited by 1 · see citing works
Wang, M. (2011) · The Enzymes · doi:10.1016/b978-0-12-415922-8.00011-2
Self-citationGu, X., Casey, P. J., & Wang, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.10.669587
Self-citationOncogene Function in Pre-Leukemia Stage of INV(16) Acute Myeloid Leukemia: A Dissertation
Xue, L. (2014) · eScholarship@UMassChan · doi:10.13028/m2d88n
Karthikeyan, S., Casey, P. J., & Wang, M. (2022) · Figshare · doi:10.6084/m9.figshare.21430854
Self-citationBindingDB (2026) · UC San Diego · doi:10.7270/q26w9gxr
- Authors
- Wang, M., Hossain, M. S., Tan, W., Coolman, B., Zhou, J., Liu, S., & Casey, P. J.
- Affiliations
- National University of Singapore (SG)
- Duke Medical Center (US)
- Corresponding author
- Wang, M
- Venue
- Oncogene
- Published
- 2010-07-12
- Volume
- 29
- Issue
- 35
- Pages
- 4959-4970
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1974673851
- Cited by
- 75
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 2 · 2014: 9 · 2013: 5 · 2012: 2
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- autophagy, apoptosis, prenylated proteins, ATG5, Atg1, HepG2 cells, tumor growth inhibition, anticancer agents, mouse embryonic fibroblasts
- MeSH terms
- Autophagy-Related Protein 5, Animals, Autophagy, Cell Cycle, Enzyme Inhibitors, Fibroblasts, Humans, Indoles, Microtubule-Associated Proteins, Neoplasms, Protein Methyltransferases, Apoptosis, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Proliferation, Mice
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