VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer

被引：22

作者：

Chen, Yiyu ^{[1
,2
]}

Liu, Zhen ^{[3
]}

Wang, Huijun ^{[2
]}

Tang, Zibo ^{[1
]}

Liu, Yiyi ^{[1
]}

Liang, Zixi ^{[1
]}

Deng, Xiaojie ^{[1
]}

Zhao, Mengyang ^{[1
]}

Fu, Qiaofen ^{[1
]}

Li, Libo ^{[1
]}

Cai, Hongbing ^{[1
]}

Xie, Weibing ^{[2
]}

Fang, Weiyi ^{[1
]}

机构：

[1] Southern Med Univ, Integrated Hosp Tradit Chinese Med, Canc Ctr, Guangzhou 510515, Guangdong, Peoples R China

[2] Southern Med Univ, Sch Forens Med, Guangzhou, Guangdong, Peoples R China

[3] Guangzhou Med Univ, Sch Basic Med Sci, Key Lab Prot Modificat & Degradat, Affiliated Canc Hosp & Inst, Guangzhou, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF CANCER | 2020年 / 146卷 / 02期

基金：

中国国家自然科学基金;

关键词：

VPS33B; NESG1; EGFR; RAS; ERK; c-Myc; p53; miR-133a-3p feedback loop; chemical carcinogens; colorectal cancer; RENAL DYSFUNCTION; GROWTH; PATHWAY; ARTHROGRYPOSIS; MECHANISM; CARCINOMA; MIGRATION; DIAGNOSIS; INVASION; SMOKING;

D O I：

10.1002/ijc.32429

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) -induced CRC mice models and nicotine-treated CRC cells via the PI3K/AKT/c-Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and the downstream cell cycle or EMT-related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c-Jun-mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c-Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B-modulating signal in VPS33B-overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and thus suppress the malignant phenotype of CRC.

引用

页码：496 / 509

页数：14

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