VPS33B suppresses lung adenocarcinoma metastasis and chemoresistance to cisplatin.
VPS33B suppresses lung adenocarcinoma metastasis and chemoresistance to cisplatin.
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DOI：
10.1016/j.gendis.2019.12.009
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发表时间：
2021-05
期刊：
影响因子：
6.8
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Liu Z;Liu J;Li Y;Wang H;Liang Z;Deng X;Fu Q;Fang W;Xu P
VPS33B在肿瘤中的存在鲜有报道。VPS33B蛋白表达下调是促进肺腺癌（LUAD）发病的不利因素。在体内和体外实验中，过表达VPS33B可减少LUAD细胞对顺铂（DDP）的迁移、侵袭、转移和化疗耐药。机制分析表明，VPS33B首先抑制表皮生长因子受体（EGFR） Ras/ERK信号，从而进一步降低致癌因子c-Myc的表达。下调的c-Myc表达降低了它结合p53启动子的速率，减弱了它的转录抑制作用；因此，c-Myc减少刺激p53表达，导致上皮-间质转化（EMT）信号减少。NESG1已被证明是非小细胞肺癌（NSCLC）的不利指标。在这里，NESG1被鉴定为VPS33B的相互作用蛋白。此外，NESG1被发现通过减少RAS/ERK/c- jun介导的转录抑制与VPS33B相互刺激。NESG1敲低激活EGFR/Ras/ERK/c-Myc信号，进一步下调p53表达，从而激活EMT信号，促进LUAD的迁移和侵袭。最后，我们观察到尼古丁通过诱导PI3K/AKT/c- jun介导的转录抑制来抑制VPS33B的表达。我们的研究表明VPS33B作为肿瘤抑制因子在LUAD的发病过程中发挥着重要作用。
The presence of VPS33B in tumors has rarely been reported. Downregulated VPS33B protein expression is an unfavorable factor that promotes the pathogenesis of lung adenocarcinoma (LUAD). Overexpressed VPS33B was shown to reduce the migration, invasion, metastasis, and chemoresistance of LUAD cells to cisplatin (DDP) in vivo and in vitro. Mechanistic analyses have indicated that VPS33B first suppresses epidermal growth factor receptor (EGFR) Ras/ERK signaling, which further reduces the expression of the oncogenic factor c-Myc. Downregulated c-Myc expression reduces the rate at which it binds the p53 promoter and weakens its transcription inhibition; therefore, decreased c-Myc stimulates p53 expression, leading to decreased epithelial-to-mesenchymal transition (EMT) signal. NESG1 has been shown to be an unfavorable indicator of non-small-cell lung cancer (NSCLC). Here, NESG1 was identified as an interactive protein of VPS33B. In addition, NESG1 was found to exhibit mutual stimulation with VPS33B via reduced RAS/ERK/c-Jun-mediated transcription repression. Knockdown of NESG1 activated EGFR/Ras/ERK/c-Myc signaling and further downregulated p53 expression, which thus activated EMT signaling and promoted LUAD migration and invasion. Finally, we observed that nicotine suppressed VPS33B expression by inducing PI3K/AKT/c-Jun-mediated transcription suppression. Our study demonstrates that VPS33B as a tumor suppressor is significantly involved in the pathogenesis of LUAD.
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DOI：
10.1159/000015571
发表时间：
2000-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
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作者：
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