LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer

被引：24

作者：

Li, Qiuhui ^{[1
,2
,3
,4
]}

Liu, Bigang ^{[4
]}

Chao, Hsueh-Ping ^{[4
]}

Ji, Yibing ^{[1
]}

Lu, Yue ^{[4
]}

Mehmood, Rashid ^{[1
]}

Jeter, Collene ^{[4
]}

Chen, Taiping ^{[4
]}

Moore, John R. ^{[4
]}

Li, Wenqian ^{[4
]}

Liu, Can ^{[4
]}

Rycaj, Kiera ^{[1
,4
]}

Tracz, Amanda ^{[1
]}

Kirk, Jason ^{[1
]}

Calhoun-Davis, Tammy ^{[4
]}

Xiong, Jie ^{[1
,4
]}

Deng, Qu ^{[1
,4
]}

Huang, Jiaoti ^{[5
]}

Foster, Barbara A. ^{[1
]}

Gokhale, Abhiram ^{[1
]}

Chen, Xin ^{[1
,4
,6
]}

Tang, Dean G. ^{[1
,4
,7
]}

机构：

[1] Roswell Park Comprehens Canc Ctr, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA

[2] Wuhan Univ, Sch & Hosp Stomatol, State Key Lab Breeding Base Basic Sci Stomatol Hu, Wuhan 430079, Hubei, Peoples R China

[3] Wuhan Univ, Sch & Hosp Stomatol, Key Lab Oral Biomed, Minist Educ KLOBM, Wuhan 430079, Hubei, Peoples R China

[4] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Sci Pk, Smithville, TX 78957 USA

[5] Duke Univ, Dept Pathol, Sch Med, Durham, NC 27710 USA

[6] HUST, Tongji Med Sch, Tongji Hosp, Dept Oncol, Wuhan 430030, Hubei, Peoples R China

[7] Tongji Univ, East Hosp, Res Ctr Translat Med, Canc Stem Cell Inst,Sch Med, Shanghai 200120, Peoples R China

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

ERBB NEGATIVE REGULATOR; STEM-CELL MARKER; GROWTH SUPPRESSOR; EPITHELIAL-CELLS; UP-REGULATION; EXPRESSION; GENE; PROTEIN; OVEREXPRESSION; POPULATION;

D O I：

10.1038/s41467-019-13532-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

LRIG1 has been reported to be a tumor suppressor in gastrointestinal tract and epidermis. However, little is known about the expression, regulation and biological functions of LRIG1 in prostate cancer (PCa). We find that LRIG1 is overexpressed in PCa, but its expression correlates with better patient survival. Functional studies reveal strong tumor-suppressive functions of LRIG1 in both AR(+) and AR(-) xenograft models, and transgenic expression of LRIG1 inhibits tumor development in Hi-Myc and TRAMP models. LRIG1 also inhibits castration-resistant PCa and exhibits therapeutic efficacy in pre-established tumors. We further show that 1) AR directly transactivates LRIG1 through binding to several AR-binding sites in LRIG1 locus, and 2) LRIG1 dampens ERBB expression in a cell type-dependent manner and inhibits ERBB2-driven tumor growth. Collectively, our study indicates that LRIG1 represents a pleiotropic AR-regulated feedback tumor suppressor that functions to restrict oncogenic signaling from AR, Myc, ERBBs, and, likely, other oncogenic drivers.

引用

页数：19

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