- Main
CXCL12γ Promotes Development of Metastatic Castration Resistant Prostate Cancer by Induction of Cancer Stem Cell and Neuroendocrine Phenotypes
Published Web Location
https://doi.org/10.1158/0008-5472.can-17-2332Abstract
There is evidence that cancer stem-like cells (CSC) and neuroendocrine behavior play critical roles in the pathogenesis and clinical course of metastatic castration-resistant prostate cancer (m-CRPC). However, there is limited mechanistic understanding of how CSC and neuroendocrine phenotypes impact the development of m-CRPC. In this study, we explored the role of the intracellular chemokine CXCL12γ in CSC induction and neuroendocrine differentiation and its impact on m-CRPC. CXCL12γ expression was detected in small-cell carcinoma of metastatic tissues and circulating tumor cells from m-CRPC patients and in prostate cancer cells displaying an neuroendocrine phenotype. Mechanistic investigations demonstrated that overexpression of CXCL12γ induced CSC and neuroendocrine phenotypes in prostate cancer cells through CXCR4-mediated PKCα/NFκB signaling, which promoted prostate tumor outgrowth, metastasis, and chemoresistance in vivo Together, our results establish a significant function for CXCL12γ in m-CRPC development and suggest it as a candidate therapeutic target to control aggressive disease.Significance: Expression of CXCL12γ induces the expression of a cancer stem cell and neuroendocrine phenotypes, resulting in the development of aggressive m-CRPC. Cancer Res; 78(8); 2026-39. ©2018 AACR.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.