Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B

By Yu Sun, J. Campisi, Celestia S. Higano, T. Beer, P. Porter, Ilsa M Coleman, L. True, P. Nelson. Nature Medicine, 2012

772 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/60d8d99177d2379bf309c4da367dc0e458d74f75

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Citations in the corpus

Cellular senescence promotes adverse effects of chemotherapy and cancer relapse (2016, background): “Finally, we believe these results are in line with other results suggesting that cytotoxic chemotherapy induces senescence in humans (10, 12, 27, 31).”
New horizons in tumor microenvironment biology: challenges and opportunities (2015, background): “pathway in adjacent cancer epithelial cells, thus markedly attenuating the effects of cytotoxic chemotherapy [39].”
Stroma Cells in Tumor Microenvironment and Breast Cancer (2012, positive): “Moreover, the β-catenin inhibitor XAV939 and NF-KB mutation can reverse the sensitivity to MIT [81], which is also observed in prostate cancer and ovary cancer [81].”
Aging, Cellular Senescence, and Cancer (2012, background): “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).”
The p53 protein and its molecular network: modelling a missing link between DNA damage and cell fate. (2014, background): “, WNT16B, that promote tumour growth and survival of cancer cells after cytotoxic therapy, and further reduce chemotherapy sensitivity in tumour cells, resulting in tumour progression; otherwise said, among other constraints, one must take into account the fact that chemotherapy itself can positivel”
Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “Anticancer treatments undeniably impact transcriptional response in the tumor microenvironment and cancer cells, sometimes with important impact on subsequent response to chemotherapy (for example through p53 gene down-regulation or WNT16B expression) [23, 24].”
EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS (2017, neutral): “[PubMed: 27487218] Sun Y, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, Nelson PS. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B.”