The Endogenous Cell-Fate Factor Dachshund Restrains Prostate Epithelial Cell Migration via Repression of Cytokine Secretion via a CXCL Signaling Module

被引：34

作者：

Chen, Ke ^{[1
,2
]}

Wu, Kongming ^{[1
,2
,3
]}

Jiao, Xuanmao ^{[1
,2
]}

Wang, Liping ^{[1
,2
]}

Ju, Xiaoming ^{[1
,2
]}

Wang, Min ^{[1
,2
]}

Di Sante, Gabriele ^{[1
,2
]}

Xu, Shaohua ^{[1
,2
]}

Wang, Qiong ^{[1
,2
]}

Li, Kevin ^{[1
,2
]}

Sun, Xin ^{[1
,2
]}

Xu, Congwen ^{[1
,2
]}

Li, Zhiping ^{[1
,2
]}

Casimiro, Mathew C. ^{[1
,2
]}

Ertel, Adam ^{[1
]}

Addya, Sankar ^{[1
]}

McCue, Peter A. ^{[2
]}

Lisanti, Michael P. ^{[2
]}

Wang, Chenguang ^{[1
,2
]}

Davis, Richard J. ^{[4
]}

Mardon, Graeme ^{[5
,6
]}

Pestell, Richard G. ^{[1
,2
,7
]}

机构：

[1] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[3] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China

[4] Neural Stem Cell Inst, Rensselaer, NY USA

[5] Baylor Coll Med, Dept Pathol & Mol, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Human Genet, Houston, TX 77030 USA

[7] Kazan Fed Univ, Kazan, Russia

来源：

CANCER RESEARCH | 2015年 / 75卷 / 10期

关键词：

ANDROGEN RECEPTOR; CYCLIN D1; INTERLEUKIN-8; DACH1; PROGRESSION; GROWTH; GENE; EXPRESSION; INDUCTION; INVASION;

D O I：

10.1158/0008-5472.CAN-14-0611

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Prostate cancer is the second leading form of cancer-related death in men. In a subset of prostate cancer patients, increased chemokine signaling IL8 and IL6 correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are produced by prostate epithelial cells and promote prostate cancer cell invasion; however, the mechanisms restraining prostate epithelial cell cytokine secretion are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited CRPC tumor growth in mice. Using Dach1(fl/fl)/Probasin-Cre bitransgenic mice, we show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to prostate epithelial cell growth and restrains migration via CXCL signaling. DACH1 inhibited expression, transcription, and secretion of the CXCL genes (IL8 and IL6) by binding to their promoter regulatory regions in chromatin. DACH1 is thus a newly defined determinant of benign and malignant prostate epithelium cellular growth, migration, and cytokine abundance in vivo. (C) 2015 AACR.

引用

页码：1992 / 2004

页数：13

共 55 条

[1] Elevated levels of circulating interleukin-6 and transforming growth factor-β1 in patients with metastatic prostatic carcinoma [J].