Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B
Open accessAbstract
Acquired resistance to anticancer treatments is a substantial barrier to reducing the morbidity and mortality that is attributable to malignant tumors. Components of tissue microenvironments are recognized to profoundly influence cellular phenotypes, including susceptibilities to toxic insults. Using a genome-wide analysis of transcriptional responses to genotoxic stress induced by cancer therapeutics, we identified a spectrum of secreted proteins derived from the tumor microenvironment that includes the Wnt family member wingless-type MMTV integration site family member 16B (WNT16B). We determined that WNT16B expression is regulated by nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB) after DNA damage and subsequently signals in a paracrine manner to activate the canonical Wnt program in tumor cells. The expression of WNT16B in the prostate tumor microenvironment attenuated the effects of cytotoxic chemotherapy in vivo, promoting tumor cell survival and disease progression. These results delineate a mechanism by which genotoxic therapies given in a cyclical manner can enhance subsequent treatment resistance through cell nonautonomous effects that are contributed by the tumor microenvironment.
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These chemoprotective SASP factors include WNT16B, IL-6, and TIMP-1.
“These chemoprotective SASP factors include WNT16B, IL-6, and TIMP-1 (tissue inhibitor of metalloproteinases-1).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [133]
The Results section ('Paracrine WNT16B attenuates the effect of cytotoxic therapy'; page unavailable) shows that WNT16B-containing conditioned medium reduced chemotherapy-induced cytotoxicity. The Discussion (page unavailable) links the damage-response secretory program to SASP and mentions IL-6, but describes IL-6 as reinforcing senescence and immune responses, not as chemoprotective. The copy does not establish TIMP-1 as a chemoprotective SASP factor (searched: TIMP-1, TIMP1, tissue inhibitor of metalloproteinases). (LLM, conf=0.87)
Experimental — accuracy not yet measuredSenescent cells, particularly those that senesce in response to DNA-damaging radiation or chemotherapeutic agents, secrete factors that can protect neighboring tumor cells from being killed by those same chemotherapeutic agents.
“Even more ironic is the finding that senescent cells, particularly those that senesce in response to DNA-damaging radiation or chemotherapeutic agents, secrete factors that can protect neighboring tumor cells from being killed by those same chemotherapeutic agents (133, 134).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [133]
The Results section (‘Therapy induces damage responses in tumor microenvironments’; page unavailable) reports that chemotherapy or radiation increased extracellular WNT16B from prostate fibroblasts. ‘Paracrine WNT16B attenuates the effect of cytotoxic therapy’ reports improved tumor-cell survival and reduced apoptosis during mitoxantrone treatment. The Discussion links the damage-response secretome to a senescence phenotype, but the cited experiments do not establish that the protective fibroblasts had themselves become senescent. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThese changes can aid development of therapy resistance and contribute to undesirable side effects.
“These changes can aid the development of therapy resistance78–80 and contribute to undesirable side effects80.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [79]
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Cites
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931 · see citing works
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568 · see citing works
Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
Peinado, H., Olmeda, D., & Cano, A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2131 · Cited by 3,121 · see citing works
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · see citing works
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160 · see citing works
Drug Resistance and the Solid Tumor Microenvironment
Tredan, O., Galmarini, C. M., Patel, K., & Tannock, I. F. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm135 · Cited by 2,116 · see citing works
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 · see citing works
Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling
Huang, S.-M. A., Mishina, Y., Liu, S.-M., Cheung, A. K., Stegmeier, F., Michaud, G., Charlat, O., Wiellette, E., Zhang, Y., Wiessner, S., et al. (2009) · Nature · doi:10.1038/nature08356 · Cited by 2,077 · see citing works
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · see citing works
DeNardo, D. G., Brennan, D. J., Rexhepaj, E., Ruffell, B., Shiao, S. L., Madden, S. F., Gallagher, W. M., Wadhwani, N., Keil, S. D., Junaid, S. A., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8274.cd-10-0028 · Cited by 1,715 · see citing works
Molecular mechanisms of drug resistance
Longley, D., & Johnston, P. (2005) · The Journal of Pathology · doi:10.1002/path.1706 · Cited by 1,686 · see citing works
Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
Sakai, W., Swisher, E. M., Karlan, B. Y., Agarwal, M. K., Higgins, J., Friedman, C., Villegas, E., Jacquemont, C., Farrugia, D. J., Couch, F. J., et al. (2008) · Nature · doi:10.1038/nature06633 · Cited by 1,086 · see citing works
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046 · see citing works
Senescence-messaging secretome: SMS-ing cellular stress
Kuilman, T., & Peeper, D. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2560 · Cited by 909 · see citing works
Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M., & Green, M. R. (2008) · Cell · doi:10.1016/j.cell.2007.12.032 · Cited by 903 · see citing works
Repopulation of cancer cells during therapy: an important cause of treatment failure
Kim, J. J., & Tannock, I. F. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1650 · Cited by 690 · see citing works
A Wnt–Axin2–GSK3β cascade regulates Snail1 activity in breast cancer cells
Yook, J. I., Li, X.-Y., Ota, I., Hu, C. Y., Kim, H. S., Kim, N. H., Cha, S. Y., Ryu, J. K., Choi, Y. J., Kim, J., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1508 · Cited by 617 · see citing works
Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence
Coppé, J.-P., Kauser, K., Campisi, J., & Beauséjour, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603307200 · Cited by 604 · see citing works
Self-citationMacrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer
Shree, T., Olson, O. C., Elie, B. T., Kester, J. C., Garfall, A. L., Simpson, K., Bell-McGuinn, K. M., Zabor, E. C., Brogi, E., & Joyce, J. A. (2011) · Genes & Development · doi:10.1101/gad.180331.111 · Cited by 541 · see citing works
The Bone Marrow Microenvironment as a Tumor Sanctuary and Contributor to Drug Resistance
Meads, M. B., Hazlehurst, L., & Dalton, W. S. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-2223 · Cited by 519 · see citing works
Bavik, C., Coleman, I., Dean, J. P., Knudsen, B., Plymate, S., & Nelson, P. S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1716 · Cited by 453 · see citing works
Self-citationDNA Damage-Mediated Induction of a Chemoresistant Niche
Gilbert, L. A., & Hemann, M. T. (2010) · Cell · doi:10.1016/j.cell.2010.09.043 · Cited by 428 · see citing works
Cell-cycle arrest versus cell death in cancer therapy
Waldman, T. A., Zhang, Y., Dillehay, L. E., Yu, J., Kinzler, K. W., Vogelstein, B., & Williams, J. (1997) · Nature Medicine · doi:10.1038/nm0997-1034 · Cited by 388 · see citing works
Biswas, S., Guix, M., Rinehart, C., Dugger, T. C., Chytil, A. M., Moses, H. L., Freeman, M. L., & Arteaga, C. L. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30740 · Cited by 346 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
Genetic analysis of chemoresistance in primary murine lymphomas
Schmitt, C. A., Rosenthal, C., & Lowe, S. W. (2000) · Nature Medicine · doi:10.1038/79542 · Cited by 280 · see citing works
Acquired multicellular-mediated resistance to alkylating agents in cancer.
Kobayashi, H., Man, S., Graham, C. H., Kapitain, S. J., Teicher, B. A., & Kerbel, R. S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3294 · Cited by 277 · see citing works
Wang, F., Hansen, R. K., Radisky, D. C., Yoneda, T., Barcellos‐Hoff, M. H., PETERSEN, O. W., Turley, E. A., & Bissell, M. J. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.19.1494 · Cited by 271 · see citing works
Vincan, E., & Barker, N. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9156-4 · Cited by 198 · see citing works
Wang, T., Diaz, L. A., Romans, K. E., Bardelli, A., Saha, S., Galizia, G., Choti, M. A., Donehower, R. C., Parmigiani, G., Shih, I., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308716101 · Cited by 183 · see citing works
Chemoresistance in solid tumours
Wilson, T. R., Longley, D. B., & Johnston, P. G. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl280 · Cited by 171 · see citing works
Resistance mechanisms to cancer chemotherapy
Redmond, K. M. (2008) · Frontiers in bioscience · doi:10.2741/3070 · Cited by 150 · see citing works
Repopulation of tumour cells between cycles of chemotherapy: a neglected factor
Davis, A. J., & Tannock, I. F. (2000) · The Lancet Oncology · doi:10.1016/s1470-2045(00)00019-x · Cited by 150 · see citing works
Chemotherapy Sensitivity and Resistance Assays: A Systematic Review
Samson, D. J., Seidenfeld, J., Ziegler, K. M., & Aronson, N. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.04.077 · Cited by 129 · see citing works
Wu, K., & Bonavida, B. (2009) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v29.i3.40 · Cited by 126 · see citing works
Alderton, P., Gross, J., & Green, M. D. (1992) · PubMed · Cited by 120 · see citing works
Croix, B. S., Rak, J. W., Kapitain, S. J., Sheehan, C., Graham, C. H., & Kerbel, R. S. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.18.1285 · Cited by 106 · see citing works
Involvement of Rel/Nuclear Factor-κB Transcription Factors in Keratinocyte Senescence
Bernard, D., Gosselin, K., Monté, D., Vercamer, C., Bouali, F., Pourtier, A., Vandenbunder, B., & Abbadie, C. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0005 · Cited by 105 · see citing works
SASPense and DDRama in cancer and ageing
Fumagalli, M., & di Fagagna, F. D. (2009) · Nature Cell Biology · doi:10.1038/ncb0809-921 · Cited by 102 · see citing works
Binet, R., Ythier, D., Robles, A. I., Collado, M., Larrieu, D., Fonti, C., Brambilla, E., Brambilla, C., Serrano, M., Harris, C. C., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1016 · Cited by 101 · see citing works
Chemotherapy response and resistance
Lee, S., & Schmitt, C. A. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00014-x · Cited by 61 · see citing works
Beer, T. M., Garzotto, M. G., Lowe, B. A., Ellis, W. J., Montalto, M. A., Lange, P. H., & Higano, C. S. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1021-03 · Cited by 39 · see citing works
Self-citationCalcium-Dependent Regulation of NEMO Nuclear Export in Response to Genotoxic Stimuli
Berchtold, C. M., Wu, Z., Huang, T. T., & Miyamoto, S. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01772-06 · Cited by 31 · see citing works
Molecular and Physiologic Mechanisms of Drug Resistance in Cancer: An Overview
Kerbel, R. S. (2001) · Cancer and Metastasis Reviews · doi:10.1023/a:1013129128673 · Cited by 30 · see citing works
Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer
Garzotto, M. G., Myrthue, A., Higano, C. S., & Beer, T. M. (2006) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2005.11.034 · Cited by 29 · see citing works
Self-citationHelmrich, A., Lee, S., O’Brien, P. C., Dörken, B., Lowe, S. W., Schröck, E., & Schmitt, C. A. (2005) · Oncogene · doi:10.1038/sj.onc.1208600 · Cited by 15 · see citing works
Flagged first, then by citations
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A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · see citing works
Emerging Biological Principles of Metastasis
Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.11.037 · Cited by 3,075 · see citing works
Aging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · see citing works
Self-citationCellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818 · see citing works
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840 · see citing works
Bertrand, N., Wu, J., Xu, X., Kamaly, N., & Farokhzad, O. C. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.11.009 · Cited by 2,865 · see citing works
Influence of tumour micro-environment heterogeneity on therapeutic response
Junttila, M. R., & de Sauvage, F. J. (2013) · Nature · doi:10.1038/nature12626 · Cited by 2,694 · see citing works
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062 · see citing works
Therapeutic Targeting of the Tumor Microenvironment
Bejarano, L., Jordão, M. J. C., & Joyce, J. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1808 · Cited by 1,670 · see citing works
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505 · see citing works
The evolutionary history of lethal metastatic prostate cancer
ICGC Prostate UK Group, Gundem, G., Loo, P. V., Kremeyer, B., Alexandrov, L. B., Tubío, J. M. C., Papaemmanuil, E., Brewer, D. S., Kallio, H. M. L., Högnäs, G., et al. (2015) · Nature · doi:10.1038/nature14347 · Cited by 1,359 · see citing works
Cellular senescence promotes adverse effects of chemotherapy and cancer relapse
Demaria, M., O'Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0241 · Cited by 1,338 · see citing works
Self-citationLaberge, R.-M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3195 · Cited by 1,160 · see citing works
Self-citationTargeting the tumour stroma to improve cancer therapy
Valkenburg, K. C., de Groot, A. E., & Pienta, K. J. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0007-1 · Cited by 1,084 · see citing works
Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?
Coussens, L. M., Zitvogel, L., & Palucka, A. K. (2013) · Science · doi:10.1126/science.1232227 · Cited by 1,070 · see citing works
CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer
Zhang, H., Deng, T., Liu, R., Ning, T., Yang, H., Liu, D., Zhang, Q., Lin, D., Ge, S., Bai, M., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01168-8 · Cited by 1,023 · see citing works
Fibroblast heterogeneity in the cancer wound
Öhlund, D., Elyada, E., & Tuveson, D. A. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20140692 · Cited by 940 · see citing works
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 · see citing works
Inflammatory microenvironment remodelling by tumour cells after radiotherapy
McLaughlin, M., Patin, E. C., Pedersen, M., Wilkins, A. C., Dillon, M. T., Melcher, A. A., & Harrington, K. J. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0246-1 · Cited by 899 · see citing works
Cancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869 · see citing works
Microenvironmental regulation of therapeutic response in cancer
Klemm, F., & Joyce, J. A. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.11.006 · Cited by 769 · see citing works
The great escape: tumour cell plasticity in resistance to targeted therapy
Boumahdi, S., & de Sauvage, F. J. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0044-1 · Cited by 756 · see citing works
Genetics and biology of prostate cancerPreprint
Wang, G., Zhao, D., Spring, D. J., & DePinho, R. A. (2018) · Genes & Development · doi:10.1101/gad.315739.118 · Cited by 758 · see citing works
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 · see citing works
Self-citationStromal cells in tumor microenvironment and breast cancer
Mao, Y., Keller, E. T., Garfield, D. H., Shen, K., & Wang, J. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9415-3 · Cited by 671 · see citing works
The role and mechanisms of action of microRNAs in cancer drug resistance
Si, W., Shen, J., Zheng, H., & Fan, W. (2019) · Clinical Epigenetics · doi:10.1186/s13148-018-0587-8 · Cited by 675 · see citing works
Moiseeva, O., Deschênes‐Simard, X., St‐Germain, E., Igelmann, S., Huot, G., Cadar, A. E., Bourdeau, V., Pollak, M. N., & Ferbeyre, G. (2013) · Aging Cell · doi:10.1111/acel.12075 · Cited by 654 · see citing works
Fiori, M. E., Franco, S. D., Villanova, L., Bianca, P., Stassi, G., & Maria, R. D. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0994-2 · Cited by 648 · see citing works
The senescence-associated secretory phenotype and its regulation
Lopes-Paciencia, S., Saint-Germain, E., Rowell, M.-C., Ruiz, A. F., Kalegari, P., & Ferbeyre, G. (2019) · Cytokine · doi:10.1016/j.cyto.2019.01.013 · Cited by 601 · see citing works
Stem cell programs in cancer initiation, progression, and therapy resistance
Huang, T., Song, X., Xu, D., Tiek, D., Goenka, A., Wu, B., Sastry, N., Hu, B., & Cheng, S.-Y. (2020) · Theranostics · doi:10.7150/thno.41648 · Cited by 524 · see citing works
A peek into cancer-associated fibroblasts: origins, functions and translational impact
LeBleu, V. S., & Kalluri, R. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.029447 · Cited by 539 · see citing works
Therapy-induced tumour secretomes promote resistance and tumour progression
Obenauf, A. C., Zou, Y., Ji, A. L., Vanharanta, S., Shu, W., Shi, H., Kong, X., Bosenberg, M., Wiesner, T., Rosen, N. X., et al. (2015) · Nature · doi:10.1038/nature14336 · Cited by 485 · see citing works
Fibroblasts in cancer: Unity in heterogeneity
Chhabra, Y., & Weeraratna, A. T. (2023) · Cell · doi:10.1016/j.cell.2023.03.016 · Cited by 488 · see citing works
Quan, T., & Fisher, G. J. (2015) · Gerontology · doi:10.1159/000371708 · Cited by 464 · see citing works
Cellular plasticity and the neuroendocrine phenotype in prostate cancer
Davies, A. H., Beltran, H., & Zoubeidi, A. (2018) · Nature Reviews Urology · doi:10.1038/nrurol.2018.22 · Cited by 431 · see citing works
Masaldan, S., Clatworthy, S. A. S., Gamell, C., Meggyesy, P. M., Rigopoulos, A.-T., Haupt, S., Haupt, Y., Denoyer, D., Adlard, P. A., Bush, A. I., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2017.08.015 · Cited by 452 · see citing works
Ishii, G., Ochiai, A., & Neri, S. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.07.007 · Cited by 431 · see citing works
Martinez-Outschoorn, U. E., Lisanti, M. P., & Sotgia, F. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.01.005 · Cited by 423 · see citing works
Tumor Microenvironment and Differential Responses to Therapy
Hirata, E., & Sahai, E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026781 · Cited by 422 · see citing works
Molecular aspects of cancer cell resistance to chemotherapy
Rebucci, M., & Michiels, C. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.02.017 · Cited by 409 · see citing works
Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting
Eun, K., Ham, S. W., & Kim, H. (2017) · BMB Reports · doi:10.5483/bmbrep.2017.50.3.222 · Cited by 388 · see citing works
Tumor microenvironment and cancer therapy resistance
Sun, Y. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.07.044 · Cited by 384 · see citing works
Self-citationEMT and MET : necessary or permissive for metastasis?
Jolly, M. K., Ware, K. E., Gilja, S., Somarelli, J. A., & Levine, H. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12083 · Cited by 371 · see citing works
Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy
Song, P., Gao, Z., Bao, Y., Chen, L., Huang, Y., Liu, Y., Dong, Q., & Wei, X. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01563-4 · Cited by 382 · see citing works
WNT signalling in prostate cancer
Murillo-Garzón, V., & Kypta, R. M. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.144 · Cited by 365 · see citing works
Hyperprogressive disease: recognizing a novel pattern to improve patient management
Champiat, S., Ferrara, R., Massard, C., Besse, B., Marabelle, A., Soria, J., & Ferté, C. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0111-2 · Cited by 360 · see citing works
Cancer associated fibroblasts: An essential role in the tumor microenvironment
Tao, L., Huang, G., Song, H., Chen, Y., & Chen, L. (2017) · Oncology Letters · doi:10.3892/ol.2017.6497 · Cited by 351 · see citing works
The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice
Xu, Q., Fu, Q., Li, Z., Liu, H., Wang, Y., Lin, X., He, R., Zhang, X., Ju, Z., Campisi, J., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00491-8 · Cited by 341 · see citing works
Self-citationCancer cell plasticity during tumor progression, metastasis and response to therapy
Pérez-González, A., Bévant, K., & Blanpain, C. (2023) · Nature Cancer · doi:10.1038/s43018-023-00595-y · Cited by 353 · see citing works
Distinctive properties of metastasis-initiating cellsPreprint
Celià-Terrassa, T., & Kang, Y. (2016) · Genes & Development · doi:10.1101/gad.277681.116 · Cited by 333 · see citing works
Toward a Better Understanding of the Complexity of Cancer Drug Resistance
Gottesman, M. M., Lavi, O., Hall, M. D., & Gillet, J. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103111 · Cited by 328 · see citing works
Loh, J.-J., & Ma, S. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.04.004 · Cited by 327 · see citing works
Daynes, R. A., Araneo, B. A., Ershler, W. B., Maloney, C., Li, G. Z., & Ryu, S. Y. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.12.5219 · Cited by 1,264 · see citing works
The role of tumor microenvironment in therapeutic resistance
Son, B., Lee, S., Youn, H., Kim, E., Kim, W., & Youn, B. (2016) · Oncotarget · doi:10.18632/oncotarget.13907 · Cited by 302 · see citing works
Non-Darwinian dynamics in therapy-induced cancer drug resistance
Pisco, A. O., Brock, A., Zhou, J., Moor, A. E., Mojtahedi, M., Jackson, D. A., & Huang, S. (2013) · Nature Communications · doi:10.1038/ncomms3467 · Cited by 289 · see citing works
Hu, K., Miao, L., Goodwin, T. J., Li, J., Liu, Q., & Huang, L. (2017) · ACS Nano · doi:10.1021/acsnano.7b01522 · Cited by 293 · see citing works
Bhat, G. R., Sethi, I., Sadida, H. Q., Rah, B., Mir, R., Algehainy, N. A., Albalawi, I. A., Masoodi, T., Subbaraj, G. K., Jamal, F., et al. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10172-z · Cited by 313 · see citing works
The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer
Akamatsu, S., Wyatt, A. W., Lin, D., Lysakowski, S., Zhang, F., Kim, S., Tse, C., Wang, K., Mo, F., Haegert, A. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.012 · Cited by 280 · see citing works
Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors
Miao, L., Lin, C. M., & Huang, L. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.017 · Cited by 264 · see citing works
Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer
Zhang, Z., Karthaus, W. R., Lee, Y. S., Gao, V. R., Wu, C., Russo, J. W., Liu, M., Mota, J. M., Abida, W. M., Linton, E. L., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.005 · Cited by 259 · see citing works
Cell Senescence: Role in Aging and Age-Related Diseases
Campisi, J., & Robert, L. (2014) · Interdisciplinary Topics in Gerontology and Geriatrics · doi:10.1159/000358899 · Cited by 240 · see citing works
Self-citationTargeting the Wnt pathway in human cancers: Therapeutic targeting with a focus on OMP-54F28
Le, P. N., McDermott, J. D., & Jimeno, A. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.08.005 · Cited by 253 · see citing works
Burt, R. J., Dey, A., Aref, S., Aguiar, M., Akarca, A. U., Bailey, K., Day, W. P., Hooper, S., Kirkwood, A. A., Kirschner, K., et al. (2019) · Blood · doi:10.1182/blood.2019001398 · Cited by 249 · see citing works
Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy
Carlson, P., Dasgupta, A., Grzelak, C. A., Kim, J., Barrett, A. S., Coleman, I. M., Shor, R. E., Goddard, E. T., Dai, J., Schweitzer, E. M., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0267-0 · Cited by 251 · see citing works
Self-citationFibroblasts in the Tumor Microenvironment: Shield or Spear?
Alkasalias, T., Moyano‐Galceran, L., Arsenian‐Henriksson, M., & Lehti, K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051532 · Cited by 243 · see citing works
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247 · see citing works
Nanoparticles for modulating tumor microenvironment to improve drug delivery and tumor therapy
Yang, S., & Gao, H. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.05.004 · Cited by 256 · see citing works
How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer
Stultz, J., & Fong, L. (2021) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-021-00340-5 · Cited by 242 · see citing works
Mechanisms of cryoablation: Clinical consequences on malignant tumors
Baust, J. G., Gage, A. A., Bjerklund Johansen, T. E., & Baust, J. M. (2014) · Cryobiology · doi:10.1016/j.cryobiol.2013.11.001 · Cited by 239 · see citing works
Esterase‐Activated Charge‐Reversal Polymer for Fibroblast‐Exempt Cancer Gene Therapy
Qiu, N., Liu, X., Zhong, Y., Zhou, Z., Piao, Y., Miao, L., Zhang, Q., Tang, J., Huang, L., & Shen, Y. (2016) · Advanced Materials · doi:10.1002/adma.201603095 · Cited by 239 · see citing works
Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap
Morton, J. J., Bird, G. A., Refaeli, Y., & Jimeno, A. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1260 · Cited by 238 · see citing works
GOLM1 modulates EGFR/RTK cell-surface recycling to drive hepatocellular carcinoma metastasis
Ye, Q.-H., Zhu, W.-W., Zhang, J.-B., Qin, Y., Lu, M., Lin, G.-L., Guo, L., Zhang, B., Lin, Z.-H., Roessler, S., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.07.017 · Cited by 228 · see citing works
Cell Death Pathways Associated with Photodynamic Therapy: An Update
Kessel, D. H., & Oleinick, N. L. (2017) · Photochemistry and Photobiology · doi:10.1111/php.12857 · Cited by 224 · see citing works
Circulating and disseminated tumor cells: harbingers or initiators of metastasis?
Dasgupta, A., Lim, A. R., & Ghajar, C. M. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12022 · Cited by 224 · see citing works
Paradoxical effects of chemotherapy on tumor relapse and metastasis promotion
D’Alterio, C., Scala, S., Sozzi, G., Roz, L., & Bertolini, G. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.019 · Cited by 224 · see citing works
Escamilla, J., Schokrpur, S., Liu, C., Priceman, S. J., Moughon, D. L., Jiang, Z. K., Pouliot, F., Magyar, C. E., Sung, J. L., Xu, J., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-0992 · Cited by 221 · see citing works
Miao, L., Newby, J., Lin, C. M., Zhang, L., Xu, F., Kim, W. Y., Forest, M. G., Lai, S. K., Milowsky, M. I., Wobker, S. E., et al. (2016) · ACS Nano · doi:10.1021/acsnano.6b02776 · Cited by 221 · see citing works
Liu, J., Chen, Q., Zhu, W., Yi, X., Yang, Y. P., Dong, Z., & Liu, Z. (2017) · Advanced Functional Materials · doi:10.1002/adfm.201605926 · Cited by 219 · see citing works
Carcinoma‐associated fibroblasts: Non‐neoplastic tumour‐promoting mesenchymal cells
Polanska, U. M., & Orimo, A. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24347 · Cited by 208 · see citing works
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 · see citing works
Self-citationCaveolae and signalling in cancer
Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. P. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3915 · Cited by 207 · see citing works
Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment
Wu, P., Gao, W. Q., Su, M., Nice, E. C., Zhang, W., Lin, J., & Xie, N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.641469 · Cited by 212 · see citing works
Feng, B., Wu, J., Shen, B., Jiang, F., & Feng, J. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02599-7 · Cited by 210 · see citing works
Ammirante, M., Shalapour, S., Kang, Y., Jamieson, C. A. M., & Karin, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416498111 · Cited by 207 · see citing works
Martinez‐Outschoorn, U., Sotgia, F., & Lisanti, M. P. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.03.002 · Cited by 208 · see citing works
Prostate organogenesis: tissue induction, hormonal regulation and cell type specification
Toivanen, R., & Shen, M. M. (2017) · Development · doi:10.1242/dev.148270 · Cited by 204 · see citing works
Cancer-associated fibroblasts: Origin, function, imaging, and therapeutic targeting
Rimal, R., Desai, P. B., Daware, R., Hosseinnejad, A., Prakash, J., Lammers, T., & Singh, S. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114504 · Cited by 201 · see citing works
Poff, A. M., Ari, C., Seyfried, T. N., & D’Agostino, D. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065522 · Cited by 191 · see citing works
Donlon, N., Power, R. F., Hayes, C., Reynolds, J. V., & Lysaght, J. (2021) · Cancer Letters · doi:10.1016/j.canlet.2020.12.045 · Cited by 189 · see citing works
PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy
Dou, X., Fu, Q., Long, Q., Liu, S., Zou, Y., Fu, D., Xu, Q., Jiang, Z., Ren, X., Zhang, G., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00912-w · Cited by 195 · see citing works
Self-citationParacrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth
Ono, M., Yin, P., Navarro, A., Moravek, M. B., Coon, J. S., Druschitz, S. A., Serna, V. A., Qiang, W., Brooks, D. C., Malpani, S. S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313650110 · Cited by 186 · see citing works
A Novel Indication for Panobinostat as a Senolytic Drug in NSCLC and HNSCC
Samaraweera, L., Adomako, A., Rodriguez-Gabin, A., & McDaid, H. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-01964-1 · Cited by 183 · see citing works
The pro-tumorigenic host response to cancer therapies
Shaked, Y. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0209-6 · Cited by 181 · see citing works
Holtzhausen, A., Zhao, F. L., Evans, K. S., Tsutsui, M., Orabona, C., Tyler, D. S., & Hanks, B. A. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0167 · Cited by 179 · see citing works
Bent, E. H., Gilbert, L. A., & Hemann, M. T. (2016) · Genes & Development · doi:10.1101/gad.284851.116 · Cited by 179 · see citing works
Nanoformulations for combination or cascade anticancer therapy
Miao, L., Guo, S., Lin, C. M., Liu, Q., & Huang, L. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.06.003 · Cited by 178 · see citing works
Lessons from patient-derived xenografts for better in vitro modeling of human cancer
Choi, S. Y. C., Lin, D., Gout, P. W., Collins, C. C., Xu, Y., & Wang, Y. Z. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.009 · Cited by 174 · see citing works
Co-evolution of Matrisome and Adaptive Adhesion Dynamics Drives Ovarian Cancer Chemoresistance
Pietilä, E. A., Gonzalez-Molina, J., Moyano-Galceran, L., Jamalzadeh, S., Zhang, K., Lehtinen, L., Turunen, S. P., Martins, T. A., Gultekin, O., Lamminen, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24009-8 · Cited by 175 · see citing works
Stoyanova, T., Cooper, A. R., Drake, J., Liu, X., Armstrong, A., Pienta, K., Zhang, H., Kohn, D., Huang, J.-T., Witte, O., et al. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1320565110 · Cited by 170 · see citing works
Biological Effects of Nanoparticles on Macrophage Polarization in the Tumor Microenvironment
Reichel, D., Tripathi, M., & Perez, J. M. (2018) · Nanotheranostics · doi:10.7150/ntno.30052 · Cited by 172 · see citing works
- Authors
- Sun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L., & Nelson, P. S.
- Affiliations
- Fred Hutch Cancer Center (US)
- Buck Institute for Research on Aging (US)
- University of Washington (US)
- Oregon Health & Science University (US)
- Corresponding author
- Nelson, Peter S
- ORCID
- Venue
- Nature Medicine
- Published
- 2012-08-05
- Volume
- 18
- Issue
- 9
- Pages
- 1359-1368
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3677971
- OpenAlex
- W1985549756
- Cited by
- 793
- References
- 46
- Citations by year
- 2026: 31 · 2025: 35 · 2024: 48 · 2023: 58 · 2022: 60 · 2021: 69 · 2020: 62 · 2019: 57 · 2018: 61 · 2017: 67 · 2016: 60 · 2015: 54 · 2014: 61 · 2013: 61 · 2012: 8
- FWCI
- 23.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p50ca083636-15)
- U.S. Public Health Service (U54126540)
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- National Cancer Institute (P50-CA083636, P50 CA83636, P50CA138293, U54CA126540, U01CA164188, R01CA119125, P50CA097186)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- prostate cancer, tumor microenvironment, chemoresistance, NF-κB signaling, genotoxic stress, paracrine signaling, Wnt/β-catenin signaling, tumor cell survival
- MeSH terms
- Analysis of Variance, Animals, B-Lymphocytes, Cell Line, DNA Damage, Humans, Immunohistochemistry, Male, Prostatic Neoplasms, NF-kappa B, Mice, SCID, Drug Resistance, Neoplasm, Gene Expression Profiling, Wnt Proteins, Mice, Tumor Microenvironment, Wnt Signaling Pathway
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