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

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机构： [1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China [2]School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, China [3]Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China

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关键词： VPS33B NESG1 EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop chemical carcinogens colorectal cancer

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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. © 2019 UICC.

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出版当年[2019]版：

大类 | 2 区

医学

小类 | 2 区肿瘤学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区肿瘤学

第一作者：

第一作者机构： [1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China [2]School of Forensic Medicine, Southern Medical University, Guangzhou, Guangdong, China

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通讯机构： [1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China [*1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China

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