The DOI matches its Crossref record; 44 of the 46 references it cites were found in a registry or an index.
p38MAPK Plays a Crucial Role in Stromal-Mediated Tumorigenesis
Open accessPublished version of a preprint
Abstract
Neoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importance in tumorigenesis, the mechanisms that control TME-derived factor expression remain poorly understood. Here, we address a key unanswered question: how the SASP is sustained in senescent fibroblasts and CAFs. We find that the mitogen-activated protein kinase p38 (p38MAPK) controls AUF1 occupancy on SASP mRNAs and thus controls their stability. The importance of this regulatory mechanism is underscored by our findings that stromal-specific p38MAPK inhibition abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Our data suggest that targeting SASP mRNA stability through inhibition of p38MAPK will significantly aid the development of clinical strategies to target the TME. Significance: The TME plays a key role in tumorigenesis. We demonstrate that p38MAPK governs a posttranscriptional mechanism that sustains the protumorigenic SASP. Inhibition of p38MAPK abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Thus, p38MAPK is a TME-specific Achilles' heel that may be exploited as a new therapeutic target. Cancer Discov; 4(6); 716–29. ©2014 AACR. See related commentary by Isacke and Barcellos-Hoff, p. 637 This article is highlighted in the In This Issue feature, p. 621
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759
Mesenchymal stem cells within tumour stroma promote breast cancer metastasis
Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., Richardson, A. L., Polyak, K., Tubo, R., & Weinberg, R. A. (2007) · Nature · doi:10.1038/nature06188 · Cited by 3,206
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
Protein kinases — the major drug targets of the twenty-first century?
Cohen, P. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd773 · Cited by 2,232
Cuenda, A., Rouse, J., Doza, Y. N., Meier, R., Cohen, P., Gallagher, T. F., Young, P. R., & Lee, J. C. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00357-f · Cited by 2,086
Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · cited 3×
“The regulation of SASP expression is complex, involving the DNA damage response (16), HDAC1 activity (15), and transcriptional regulation by NF B and C/EBP (17) (18) (19).”
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
Stromal gene expression predicts clinical outcome in breast cancer
Finak, G., Bertos, N., Pepin, F., Sadekova, S., Souleimanova, M., Zhao, H., Chen, H., Ömeroğlu, G., Meterissian, S. H., Ömeroğlu, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1764 · Cited by 1,707
Cited by
Sorted by citations
Cellular senescence: the good, the bad and the unknown
Huang, W., Hickson, L. J., Eirin, A., Kirkland, J. L., & Lerman, L. O. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00601-z · Cited by 1,150
Unmasking Transcriptional Heterogeneity in Senescent Cells
Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972
A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer
Braicu, C., Buse, M., Busuioc, C. I., Drulă, R., Gulei, D., Ráduly, L., Alexandru Vasile, R. U. S. U., Irimie, A., Atanasov, A. G., Slaby, O., et al. (2019) · Cancers · doi:10.3390/cancers11101618 · Cited by 940
Unmasking senescence: context-dependent effects of SASP in cancer
Faget, D. V., Ren, Q., & Stewart, S. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0156-2 · Cited by 863
Self-citationThe senescence-associated secretory phenotype and its physiological and pathological implications
Wang, B., Han, J., Elisseeff, J. H., & Demaria, M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00727-x · Cited by 948
New horizons in tumor microenvironment biology: challenges and opportunities
Chen, F., Zhuang, X., Lin, L., Yu, P., Wang, Y., Shi, Y., Hu, G., & Sun, Y. (2015) · BMC Medicine · doi:10.1186/s12916-015-0278-7 · Cited by 704
Diversity and versatility of p38 kinase signalling in health and disease
Canovas, B., & Nebreda, A. R. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00322-w · Cited by 657
Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis
Ruhland, M. K., Loza, A. J., Capietto, A.-H., Luo, X., Knolhoff, B. L., Flanagan, K. C., Belt, B. A., Alspach, E., Leahy, K., Luo, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms11762 · Cited by 496
Self-citationZhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 425
Tumor microenvironment and cancer therapy resistance
Sun, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.07.044 · Cited by 391
Shirure, V. S., Bi, Y., Curtis, M. B., Lezia, A., Goedegebuure, M. M., Goedegebuure, S. P., Aft, R., Fields, R. C., & George, S. C. (2018) · Lab on a Chip · doi:10.1039/c8lc00596f · Cited by 316
Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis
Curtis, M., Kenny, H. A., Ashcroft, B., Mukherjee, A., Johnson, A., Zhang, Y., Helou, Y. A., Batlle, R., Liu, X., Gutiérrez, N. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.007 · Cited by 284
Signaling pathways in cancer‐associated fibroblasts: recent advances and future perspectives
Fang, Z., Meng, Q., Xu, J., Wang, W., Zhang, B., Liu, J., Liang, C., Hua, J., Zhao, Y., Yu, X., et al. (2022) · 癌症:英文版 · doi:10.1002/cac2.12392 · Cited by 304
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247
Francescone, R., Costa, D. B. V., Franco‐Barraza, J., Wagner, J., Muir, A., Lau, A. N., Gabitova, L., Pazina, T., Gupta, S., Luong, T., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0775 · Cited by 227
Cellular senescence: the sought or the unwanted?
Sun, Y., Coppé, J.-P., & Lam, E. W.-F. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.08.002 · Cited by 208
Corre, I., Paris, F., & Huot, J. (2017) · Oncotarget · doi:10.18632/oncotarget.18264 · Cited by 195
Spatial and Temporal Control of Senescence
Ito, Y., Hoare, M., & Narita, M. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.07.004 · Cited by 178
Cellular senescence and the tumour microenvironment
Takasugi, M., Yoshida, Y., & Ohtani, N. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13268 · Cited by 190
“Social Life” of Senescent Cells: What Is SASP and Why Study It?
Borodkina, A. V., Deryabin, P. I., Giukova, А. А., & Nikolsky, N. N. (2018) · Acta Naturae · doi:10.32607/20758251-2018-10-1-4-14 · Cited by 170
Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression
Ye, J., Baer, J. M., Faget, D. V., Morikis, V. A., Ren, Q., Melam, A., Delgado, A. P., Luo, X., Bagchi, S. M., Belle, J. I., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0426 · Cited by 178
Self-citationRegulation of senescence traits by MAPKs
Anerillas, C., Abdelmohsen, K., & Gorospe, M. (2020) · GeroScience · doi:10.1007/s11357-020-00183-3 · Cited by 172
Chambers, C. R., Ritchie, S., Pereira, B., & Timpson, P. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13042 · Cited by 182
Zhang, B., Fu, D., Xu, Q., Cong, X., Wu, C., Zhong, X., Ma, Y., Lv, Z., Chen, F., Han, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04010-4 · Cited by 157
Senescence and the tumor-immune landscape: Implications for cancer immunotherapy
Chibaya, L., Snyder, J. T., & Ruscetti, M. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.005 · Cited by 146
Therapy-Induced Senescence Drives Bone Loss
Yao, Z., Murali, B., Ren, Q., Luo, X., Faget, D. V., Cole, T., Ricci, B., Thotala, D., Monahan, J., van Deursen, J. M., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2348 · Cited by 129
Self-citationThe roles of tumor- and metastasis-promoting carcinoma-associated fibroblasts in human carcinomas
Mezawa, Y., & Orimo, A. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2471-1 · Cited by 127
Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes
Wang, T., Notta, F., Navab, R., Joseph, J., Ibrahimov, E., Xu, J., Zhu, C.-Q., Borgida, A., Gallinger, S., & Tsao, M.-S. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0192 · Cited by 123
Cancer-associated fibroblasts support vascular growth through mechanical force
Sewell-Loftin, M. K., Bayer, S. V. H., Crist, E., Hughes, T., Joison, S. M., Longmore, G. D., & George, S. C. (2017) · Scientific Reports · doi:10.1038/s41598-017-13006-x · Cited by 123
Sun, Y., Zhu, D., Chen, F., Qian, M., Wei, H., Chen, W., & Xu, J. (2016) · Oncogene · doi:10.1038/onc.2015.494 · Cited by 112
RetractedThe p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer
García-Hernández, L., García‐Ortega, M. B., Ruiz-Alcalá, G., Carrillo, E., Marchal, J. A., & García, M. Á. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010370 · Cited by 111
Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors
Meharena, H. S., Marco, A., Dileep, V., Lockshin, E. R., Akatsu, G. Y., Mullahoo, J., Watson, L. A., Ko, T., Guerin, L. N., Abdurrob, F., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2021.12.002 · Cited by 92
Zhang, X., Liu, X., Du, Z., Wei, L., Fang, H., Dong, Q., Niu, J., Li, Y., Gao, J. T., Zhang, M. Q., et al. (2021) · Genome Research · doi:10.1101/gr.275235.121 · Cited by 103
Zhao, S., Guan, B., Mi, Y., Shi, D., Wei, P., Gu, Y., Cai, S., Xu, Y., Li, X., Yan, D., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01859-6 · Cited by 94
Cancer secretome and inflammation: The bright and the dark sides of NF-κB
Capece, D., Verzella, D., Tessitore, A., Alesse, E., Capalbo, C., & Zazzeroni, F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.08.004 · Cited by 94
Hagerling, C., Owyong, M., Sitarama, V., Wang, C., Lin, C., van den Bijgaart, R. J. E., Koopman, C. D., Brenot, A., Nanjaraj, A., Wärnberg, F., et al. (2020) · BMC Cancer · doi:10.1186/s12885-020-06986-z · Cited by 91
Poppler, L. H., Ee, X., Schellhardt, L., Hoben, G. M., Pan, D., Hunter, D. A., Yan, Y., Moore, A. M., Snyder‐Warwick, A. K., Stewart, S. A., et al. (2016) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0003 · Cited by 87
Self-citationImmune Aging and Immunotherapy in Cancer
Kaiser, M., Semeraro, M. D., Herrmann, M., Absenger, G., Gerger, A., & Renner, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137016 · Cited by 79
CHEN, Q., Li, P., Li, P., Xu, Y., LI, Y., & TANG, B. (2014) · Oncology Reports · doi:10.3892/or.2014.3626 · Cited by 75
RetractedGiroud, J., Bouriez, I., Paulus, H., Pourtier, A., Debacq‐Chainiaux, F., & Pluquet, O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310788 · Cited by 87
Toste, P. A., Nguyen, A. H., Kadera, B. E., Duong, M., Wu, N., Elliott, I. A., Tran, L. M., Bikhchandani, M., Li, L., Patel, S. G., et al. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0348 · Cited by 74
Gui, J., Zahedi, F., Ortiz, A., Cho, C., Katlinski, K. V., Alicea-Torres, K. M., Li, J., Todd, L., Zhang, H., Beiting, D. P., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0064-0 · Cited by 70
Murali, B., Ren, Q., Luo, X., Faget, D. V., Wang, C., Johnson, R. M., Gruosso, T., Flanagan, K. C., Fu, Y., Leahy, K., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0234 · Cited by 67
Self-citationThe controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy
Cao, L., Li, K., Li, Q., Tong, Q., Wang, Y., & Huang, L. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02475-8 · Cited by 79
Senescent stromal cells: roles in the tumor microenvironment
Gabai, Y., Assouline, B., & Ben‐Porath, I. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.09.002 · Cited by 67
Beach, J. A., Aspuria, P.-J. P., Cheon, D., Lawrenson, K., Agadjanian, H., Walsh, C., Karlan, B. Y., & Oršulić, S. (2015) · Oncotarget · doi:10.18632/oncotarget.6703 · Cited by 62
Senescence and cancer: An evolving inflammatory paradox
Ruhland, M. K., Coussens, L. M., & Stewart, S. A. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.10.001 · Cited by 62
Self-citationWerden, S. J., Sphyris, N., Sarkar, T. R., Paranjape, A. N., LaBaff, A. M., Taube, J. H., Hollier, B. G., Ramirez‐Peña, E., Soundararajan, R., den Hollander, P., et al. (2016) · Oncogene · doi:10.1038/onc.2016.203 · Cited by 59
p38MAPK builds a hyaluronan cancer niche to drive lung tumorigenesisPreprint
Brichkina, A. I., Bertero, T., Loh, H. M., Nguyen, N. T. M., Emelyanov, A., Rigade, S., Ilié, M., Hofman, P. M., Gaggioli, C., & Bulavin, D. V. (2016) · Genes & Development · doi:10.1101/gad.290346.116 · Cited by 58
The Jekyll and Hyde of Cellular Senescence in Cancer
Demirci, D., Dayanc, B., Mazi, F. A., & Şentürk, Ş. (2021) · Cells · doi:10.3390/cells10020208 · Cited by 62
Crosstalk between CAFs and tumour cells in head and neck cancer
Li, X., González-Maroto, C., & Tavassoli, M. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02053-9 · Cited by 61
Cellular senescence: mechanisms and relevance to cancer and aging
Yamauchi, S., & Takahashi, A. (2024) · The Journal of Biochemistry · doi:10.1093/jb/mvae079 · Cited by 63
Identification of stable senescence‐associated reference genes
Hernandez‐Segura, A., Rubingh, R., & Demaria, M. (2019) · Aging Cell · doi:10.1111/acel.12911 · Cited by 54
Senescent peritoneal mesothelium creates a niche for ovarian cancer metastases
Mikuła‐Pietrasik, J., Uruski, P., Sosińska, P., Maksin, K., Piotrowska‐Kempisty, H., Kucińska, M., Murias, M., Szubert, S., Woźniak, A., Szpurek, D., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.417 · Cited by 54
Therapy-induced senescence as a component of tumor biology: Evidence from clinical cancer
Saleh, T., Bloukh, S., Hasan, M., & Shboul, S. A. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188994 · Cited by 55
Cellular senescence in the tumor microenvironment and context‐specific cancer treatment strategies
Yasuda, T., Baba, H., & Ishimoto, T. (2021) · FEBS Journal · doi:10.1111/febs.16231 · Cited by 53
Liu, Q., Li, J., Sun, X., Lin, J., Yu, Z., Xiao, Y., Li, D., Sun, B., Bao, H., & Liu, Y. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01735-w · Cited by 57
The senescence-associated secretory phenotype: Fueling a wound that never heals
Pulido, T., Velarde, M. C., & Alimirah, F. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111561 · Cited by 54
Malignancy and IFITM3: Friend or Foe?
Rajapaksa, U., Chen, J., & Dong, T. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.593245 · Cited by 49
Wu, Z., Yu, Y., Liu, C., Xiong, Y., Montani, J., Yang, Z., & Ming, X. (2015) · Aging · doi:10.18632/aging.100722 · Cited by 46
Min, J., Feng, Q., Liao, W., Liang, Y., Gong, C., Li, E., He, W., Yuan, R., & Wu, L. (2018) · FEBS Open Bio · doi:10.1002/2211-5463.12479 · Cited by 46
RetractedSenescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease
Rivas, M., Gupta, G., Costanzo, L., Ahmed, H., Wyman, A. E., & Geraghty, P. M. (2022) · Medicina · doi:10.3390/medicina58060817 · Cited by 47
Cellular senescence in cancer: molecular mechanisms and therapeutic targets
Jin, P., Duan, X., Li, L., Zhou, P., Zou, C., & Xie, K. (2024) · MedComm · doi:10.1002/mco2.542 · Cited by 51
Limoge, M., Safina, A. F., Truskinovsky, A. M., Aljahdali, I. A. M., Zonneville, J., Gruevski, A., Arteaga, C. L., & Bakin, A. V. (2017) · Oncotarget · doi:10.18632/oncotarget.18755 · Cited by 44
Klepacki, H., Kowalczuk, K., Łepkowska, N., & Hermanowicz, J. M. (2025) · Cells · doi:10.3390/cells14130942 · Cited by 49
Senescence and Immunoregulation in the Tumor Microenvironment
Ruhland, M. K., & Alspach, E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.754069 · Cited by 45
Self-citationMorgan, D., Berggren, K. L., Spiess, C., Smith, H. M., Tejwani, A., Weir, S. J., Lominska, C. E., Thomas, S. M., & Gan, G. N. (2021) · Molecular Carcinogenesis · doi:10.1002/mc.23348 · Cited by 42
Deconstructing tumor heterogeneity: the stromal perspective
Vickman, R. E., Faget, D. V., Beachy, P. A., Beebe, D. J., Bhowmick, N. A., Cukierman, E., Deng, W.-M., Granneman, J. G., Hildesheim, J., Kalluri, R., et al. (2020) · Oncotarget · doi:10.18632/oncotarget.27736 · Cited by 43
Self-citationActivatable senoprobes and senolytics: Novel strategies to detect and target senescent cells
Morsli, S., Doherty, G. J., & Muñoz‐Espín, D. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111618 · Cited by 41
Amphiregulin in Cancer: New Insights for Translational Medicine
Xu, Q., Chiao, P. J., & Sun, Y. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.02.002 · Cited by 40
Roy, S., Roy, S., Kar, M., Padhi, S., Saha, A., Anuja, K., & Banerjee, B. (2018) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.12707 · Cited by 39
Meng, Q., Luo, X., Chen, J., Wang, D., Chen, E., Zhang, W., Zhang, G., Zhou, W., Xu, J., & Song, Z. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188443 · Cited by 38
Self-citationRecent advances in senescence-associated secretory phenotype and osteoporosis
Fan, H., Qiao, Z., Li, J., Shang, G., Shang, C., Chen, S., Leng, Z., Su, H., Kou, H., & Liu, H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25538 · Cited by 42
Rai, A., Greening, D. W., Xu, R., Suwakulsiri, W., & Simpson, R. J. (2020) · PROTEOMICS · doi:10.1002/pmic.202000016 · Cited by 36
Fibroblast activation and senescence in oral cancer
Prime, S. S., Cirillo, N., Hassona, Y. M., Lambert, D., Paterson, I. C., Mellone, M., Thomas, G. J., James, E. N., & Parkinson, E. K. (2016) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.12456 · Cited by 40
Wang, Y., Wang, Y., Yang, M., & Ma, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111191 · Cited by 34
mTOR as a senescence manipulation target: A forked road
Saoudaoui, S., Bernard, M., Cardin, G. B., Malaquin, N., Christopoulos, A., & Rodier, F. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.02.002 · Cited by 36
The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs
Bogdanova, D. A., Kolosova, E. D., Pukhalskaia, T. V., Levchuk, K., Demidov, O. N., & Belotserkovskaya, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25074031 · Cited by 40
Titration of RAS alters senescent state and influences tumour initiation
Chan, A. S. L., Zhu, H., Narita, M., Cassidy, L. D., Young, A. R. J., Bermejo‐Rodríguez, C., Janowska, A. T., Chen, H., Gough, S., Oshimori, N., et al. (2024) · Nature · doi:10.1038/s41586-024-07797-z · Cited by 38
Senescence in cancer: Advances in detection and treatment modalities
Billimoria, R., & Bhatt, P. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115739 · Cited by 37
Cellular senescence offers distinct immunological vulnerabilities in cancer
Zhou, L., Ma, B., & Ruscetti, M. A. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.11.010 · Cited by 40
Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer
Ma, Y., Li, C., Shen, Y., Wan-hui, Y., Han, M.-X., Mu, Y.-F., & Han, F. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1533352 · Cited by 38
Developing transcriptomic signatures as a biomarker of cellular senescence
Mahmud, S., Pitcher, L. E., Torbenson, E., Robbins, P. D., Zhang, L., & Dong, X. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102403 · Cited by 37
Stress responses in stromal cells and tumor homeostasis
Vitale, I., Manic, G., Galassi, C., & Galluzzi, L. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.04.004 · Cited by 33
Apoptosis signal-regulating kinase 1 promotes inflammation in senescence and aging
Odawara, T., Yamauchi, S., & Ichijo, H. (2024) · Communications Biology · doi:10.1038/s42003-024-06386-0 · Cited by 30
RNA binding proteins in senescence: A potential common linker for age-related diseases?
Varesi, A., Campagnoli, L. I. M., Barbieri, A., Rossi, L., Ricevuti, G., Esposito, C., Chirumbolo, S., Marchesi, N., & Pascale, A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101958 · Cited by 29
Wang, J., Zhou, X., Yu, P., Yao, J., Guo, P., Xu, Q., Zhao, Y., Wang, G., Li, Q., Zhu, X., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00886-2 · Cited by 28
Alspach, E., & Stewart, S. A. (2015) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1481 · Cited by 27
Self-citationSenescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway
Li, H., Qiu, L., Liu, Q., Ma, Z., Xie, X., Luo, Y., & Wu, X. (2022) · Genes · doi:10.3390/genes13091579 · Cited by 29
c-Myb and C/EBPβ regulate OPN and other senescence-associated secretory phenotype factors
Flanagan, K. C., Alspach, E., Pazolli, E., Parajuli, S. P., Ren, Q., Arthur, L., TAPIA-CONYER, R. C., & Stewart, S. A. (2017) · Oncotarget · doi:10.18632/oncotarget.22940 · Cited by 29
Self-citationMicro-strains in the extracellular matrix induce angiogenesis
Sewell-Loftin, M. K., Katz, J. B., George, S. C., & Longmore, G. D. (2020) · Lab on a Chip · doi:10.1039/d0lc00145g · Cited by 26
Understanding cellular senescence: pathways involved, therapeutics and longevity aiding
Kumar, A., & Thirumurugan, K. (2023) · Cell Cycle · doi:10.1080/15384101.2023.2287929 · Cited by 31
Senescent Stromal Cells in the Tumor Microenvironment: Victims or Accomplices?
Ye, M., Huang, X., Wu, Q., & Liu, F. (2023) · Cancers · doi:10.3390/cancers15071927 · Cited by 27
Oncogenic Ras modulates p38 MAPK-mediated inflammatory cytokine production in glioblastoma cells
Munoz, L., Yeung, Y. T., & Grewal, T. (2016) · Cancer Biology & Therapy · doi:10.1080/15384047.2016.1139249 · Cited by 27
Non‐canonical ATM/MRN activities temporally define the senescence secretory program
Malaquin, N., Carrier-Leclerc, A., Martinez, A., Dessureault, M., Ghadaouia, S., Coppé, J., Nadeau, S., Cardin, G., Campisi, J., & Rodier, F. (2020) · EMBO Reports · doi:10.15252/embr.202050718 · Cited by 25
Huang, Y., Huang, Y., He, J., Wang, H., Luo, Y., Li, Y., Liu, J., Zhong, L., & Zhao, Y. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119231 · Cited by 24
Phytochemistry and pharmacological activities of Vaccaria hispanica (Miller) Rauschert: a review
Zhou, G., Tang, L., Wang, T., Zhou, X., Kou, Z., Wu, J., & Wang, Z. (2015) · Phytochemistry Reviews · doi:10.1007/s11101-015-9425-1 · Cited by 23
Therapy-induced senescence through the redox lens
Robert, M., Kennedy, B. K., & Crasta, K. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103228 · Cited by 27
Tackling the tumor microenvironment: what challenge does it pose to anticancer therapies?
Chen, F., Qi, X., Qian, M., Dai, Y., & Sun, Y. (2014) · Protein & Cell · doi:10.1007/s13238-014-0097-1 · Cited by 20
GALC Triggers Tumorigenicity of Colorectal Cancer via Senescent Fibroblasts
Yang, M., Jiang, Z., Yao, G., Wang, Z., Sun, J. P., Qin, H., & Zhao, H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00380 · Cited by 20
Metadata
- Authors
- Alspach, E., Flanagan, K. C., Luo, X., Ruhland, M. K., Huang, H., Pazolli, E., Donlin, M. J., Marsh, T., Piwnica-Worms, D., Monahan, J., Novack, D. V., McAllister, S. S., & Stewart, S. A.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Stewart, Sheila A.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2014-06-01
- Volume
- 4
- Issue
- 6
- Pages
- 716-729
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC4049323
- OpenAlex
- W2121507786
- Cited by
- 167
- References
- 46
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 22 · 2023: 15 · 2022: 15 · 2021: 19 · 2020: 17 · 2019: 7 · 2018: 12 · 2017: 12 · 2016: 14 · 2015: 8 · 2014: 4
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Association for Cancer Research
- Deutsches Krebsforschungszentrum
- Broad Institute
- National Cancer Institute (P50 CA94056, R01CA166284, P50CA094056, R01CA130919, T32CA113275, P30CA091842)
- National Institute of General Medical Sciences (T32GM007067)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR057235)
- National Center for Research Resources (UL1RR024992)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- p38 MAPK, senescence-associated secretory phenotype, cancer-associated fibroblasts, senescent fibroblasts, tumor microenvironment, stromal cells, mRNA stability, AUF1, post-transcriptional regulation, carcinogenesis, therapeutic target
- MeSH terms
- Heterogeneous Nuclear Ribonucleoprotein D0, Animals, Cell Line, Cells, Cultured, Female, Fibroblasts, Humans, Imidazoles, Lipopolysaccharides, Mice, Nude, Neoplasms, Pyridines, Tumor Necrosis Factor-alpha, Cellular Senescence, Heterogeneous-Nuclear Ribonucleoprotein D, Protein Kinase Inhibitors, p38 Mitogen-Activated Protein Kinases, Tumor Microenvironment
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