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学科主题临床医学
Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11 -> miRNA-541 -> androgen receptor (AR) -> MMP9 signaling
Hu, Shuai1,2,3,4,5; Li, Lei2,3,4,5; Yeh, Shuyuan2,3,4,5; Cui, Yun1; Li, Xin1; Chang, Hong-Chiang2,3,4,5; Jin, Jie1; Chang, Chawnshang2,3,4,5,6
关键词Prostate Cancer t Cells Androgen Receptor Tumor Metastasis Tumor Microenvironment
刊名MOLECULAR ONCOLOGY
2015
DOI10.1016/j.molonc.2014.07.013
9期:1页:44-57
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者NIH ; George Whipple Professorship Endowment ; Taiwan Department of Health Clinical Trial ; Research Center of Excellence ; China 973 Program ; NIH ; George Whipple Professorship Endowment ; Taiwan Department of Health Clinical Trial ; Research Center of Excellence ; China 973 Program
研究领域[WOS]Oncology
关键词[WOS]DEPRIVATION THERAPY ; STEM-CELLS ; TUMORIGENESIS ; CARCINOMA ; INFLAMMATION ; RECRUITMENT ; MICRORNAS ; SURVIVAL ; TARGETS ; TISSUE
英文摘要

Early clinical studies suggested infiltrating T cells might be associated with poor outcomes in prostate cancer (PCa) patients. The detailed mechanisms how T cells contribute to PCa progression, however, remained unclear. Here, we found PCa cells have a better capacity to recruit more CD4(+) T cells than the surrounding normal prostate cells via secreting more chemokines-CXCL9. The consequences of more recruited CD4(+) T cells to PCa might then lead to enhance PCa cell invasion. Mechanism dissection revealed that infiltrating CD4(+) T cells might function through the modulation of FGF11 -> miRNA-541 signals to suppress PCa androgen receptor (AR) signals. The suppressed AR signals might then alter the MMP9 signals to promote the PCa cell invasion. Importantly, suppressed AR signals via AR-siRNA or anti-androgen Enzalutamide in PCa cells also enhanced the recruitment of T cells and the consequences of this positive feed back regulation could then enhance the PCa cell invasion. Targeting these newly identified signals via FGF11-siRNA, miRNA-541 inhibitor or MMP9 inhibitor all led to partially reverse the enhanced PCa cell invasion. Results from in vivo mouse models also confirmed the in vitro cell lines in co-culture studies. Together, these results concluded that infiltrating CD4(+) T cells could promote PCa metastasis via modulation of FGF11 -> miRNA-541 -> AR -> MMP9 signaling. Targeting these newly identified signals may provide us a new potential therapeutic approach to better battle PCa metastasis. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

语种英语
所属项目编号CA155477 ; CA156700 ; DOH99-TD-B-111-004 ; 2012CB518305
资助者NIH ; George Whipple Professorship Endowment ; Taiwan Department of Health Clinical Trial ; Research Center of Excellence ; China 973 Program ; NIH ; George Whipple Professorship Endowment ; Taiwan Department of Health Clinical Trial ; Research Center of Excellence ; China 973 Program
WOS记录号WOS:000347863700004
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51324
专题北京大学第一临床医学院_泌尿外科
作者单位1.Peking Univ, Dept Urol, Hosp 1, Beijing 100871, Peoples R China
2.Univ Rochester, Med Ctr, Dept Pathol, George Whipple Lab Canc Res, Rochester, NY 14642 USA
3.Univ Rochester, Med Ctr, Dept Urol, George Whipple Lab Canc Res, Rochester, NY 14642 USA
4.Univ Rochester, Med Ctr, Dept Radiat Oncol, George Whipple Lab Canc Res, Rochester, NY 14642 USA
5.Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14642 USA
6.China Med Univ Hosp, Sex Hormone Res Ctr, Taichung, Taiwan
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Hu, Shuai,Li, Lei,Yeh, Shuyuan,et al. Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11 -> miRNA-541 -> androgen receptor (AR) -> MMP9 signaling[J]. MOLECULAR ONCOLOGY,2015,9(1):44-57.
APA Hu, Shuai.,Li, Lei.,Yeh, Shuyuan.,Cui, Yun.,Li, Xin.,...&Chang, Chawnshang.(2015).Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11 -> miRNA-541 -> androgen receptor (AR) -> MMP9 signaling.MOLECULAR ONCOLOGY,9(1),44-57.
MLA Hu, Shuai,et al."Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11 -> miRNA-541 -> androgen receptor (AR) -> MMP9 signaling".MOLECULAR ONCOLOGY 9.1(2015):44-57.
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