@article{e64cf2af9c7b4913a1ccd7d77cf5618c,
title = "CXCL12g promotes metastatic castration-resistant prostate cancer by inducing cancer stem cell and neuroendocrine phenotypes",
abstract = "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 CXCL12g in CSC induction and neuroendocrine differentiation and its impact on m-CRPC. CXCL12g 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 CXCL12g induced CSC and neuroendocrine phenotypes in prostate cancer cells through CXCR4-mediated PKCa/NFkB signaling, which promoted prostate tumor outgrowth, metastasis, and chemoresistance in vivo. Together, our results establish a significant function for CXCL12g in m-CRPC development and suggest it as a candidate therapeutic target to control aggressive disease. Significance: Expression of CXCL12g induces the expression of a cancer stem cell and neuroendocrine phenotypes, resulting in the development of aggressive m-CRPC.",
author = "Younghun Jung and Cackowski, {Frank C.} and Kenji Yumoto and Decker, {Ann M.} and Jingcheng Wang and Kim, {Jin Koo} and Eunsohl Lee and Yugang Wang and Chung, {Jae Seung} and Gursky, {Amy M.} and Krebsbach, {Paul H.} and Pienta, {Kenneth J.} and Morgan, {Todd M.} and Taichman, {Russell S.}",
note = "Funding Information: The authors wish to thank Taocong Jin and Sasha Meshinchi for technical and logistical support in Molecular Core and Microscopy & Image Analysis Laboratory (MIL), Comprehensive Cancer Center Microscopy Core at University of Michigan, Ann Arbor, MI. Dr. Juan C. Ramirez (National Centre for Cardiovascular Research, Spain) kindly provided pLV and pLV-CXCL12g vectors and CXCL12g antibody. This work is directly supported by the NCI (to R.S. Taich-man; CA093900 and CA163124), the Department of Defense [to R.S. Taichman (W81XW-15-1-0413 and W81XWH-14-1-0403) and T.M. Morgan (W81XWH-14-1-0287)], and the Prostate Cancer Foundation Challenge Award (to R.S. Taichman; 16CHAL05). R.S. Taichman receives support as the Major McKinley Ash Collegiate Professor. F.C. Cackowski receives support from a Career Enhancement Award, Sub-Award (F048931) of NIH/NCI Prostate Cancer Specialized Program in Research Excellence (SPORE) to Arul Chinnaiyan at the University of Michigan (F036250). Funding Information: The authors wish to thank Taocong Jin and Sasha Meshinchi for technical and logistical support in Molecular Core and Microscopy & Image Analysis Laboratory (MIL), Comprehensive Cancer Center Microscopy Core at University of Michigan, Ann Arbor, MI. Dr. Juan C. Ramirez (National Centre for Cardiovascular Research, Spain) kindly provided pLV and pLV-CXCL12g vectors and CXCL12g antibody. This work is directly supported by the NCI (to R.S. Taichman; CA093900 and CA163124), the Department of Defense [to R.S. Taichman (W81XW-15-1-0413 and W81XWH-14-1-0403) and T.M. Morgan (W81XWH-14-1-0287)], and the Prostate Cancer Foundation Challenge Award (to R.S. Taichman; 16CHAL05). R.S. Taichman receives support as the Major McKinley Ash Collegiate Professor. F.C. Cackowski receives support from a Career Enhancement Award, Sub-Award (F048931) of NIH/NCI Prostate Cancer Specialized Program in Research Excellence (SPORE) to Arul Chinnaiyan at the University of Michigan (F036250). Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",
year = "2018",
month = apr,
day = "15",
doi = "10.1158/0008-5472.CAN-17-2332",
language = "English (US)",
volume = "78",
pages = "2026--2039",
journal = "Cancer Research",
issn = "0008-5472",
number = "8",
}