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

摘要: Acquired resistance to anticancer treatments is a substantial barrier reducing the morbidity and mortality that attributable malignant tumors. Components of tissue microenvironments are recognized profoundly influence cellular phenotypes, including susceptibilities toxic insults. Using genome-wide analysis transcriptional responses genotoxic stress induced by cancer therapeutics, we identified spectrum secreted proteins derived from tumor microenvironment includes Wnt family member wingless-type MMTV integration site 16B (WNT16B). We determined WNT16B expression regulated nuclear factor κ light polypeptide gene enhancer in B cells 1 (NF-κB) after DNA damage subsequently signals paracrine manner activate canonical program cells. The prostate attenuated effects cytotoxic chemotherapy vivo, promoting cell survival disease progression. These results delineate mechanism which therapies given cyclical can enhance subsequent treatment through nonautonomous contributed microenvironment.