Poly C binding protein 1 represses autophagy through downregulation of LC3B to promote tumor cell apoptosis in starvation

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• 作者：Wenliang Zhang^a ; ^b ; ¹ ; Hongshun Shi^a ; ¹ ; Mingming Zhang^a ; Bin Liu^a ; Shuai Mao^c ; Li Li^a ; Fang Tong^a ; Guoliang Liu^e ; Shulan Yang^b ; ^{yangshl3@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Haihe Wang^a ; ^d ; ^{wanghaih@mail.sysu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; ^{1843087468@qq.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PCBP1 ; Autophagy ; Apoptosis ; LC3B ; Cancer
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：73
• 期：Complete
• 页码：127-136
• 全文大小：3157 K

文摘

Accumulating evidences indicate that poly C binding protein (PCBP1) is downregulated in various carcinomas as a tumor suppressor, but the underlying mechanism in suppression of tumorigenesis still remains elusive. Here, we found that PCBP1 overexpression attenuates tumor cell growth upon serum-free starvation. Notably, the autophagic degradation inhibitor, chloroquine, could mimic this suppressive effect in tumor cell growth. Autophagy analyses demonstrated that PCBP1 overexpression blocked autophagic flux of tumor cells under starvation conditions, while PCBP1 downregulation in turn refueled this autophagic flux, protecting cells from death. Mechanistically, PCBP1 overexpression attenuated microtubule-associated protein Light chain 3 (LC3B) mRNA stability to repress LC3B expression, resulting in the autophagy inhibition. Consequently, PCBP1 overexpression strongly triggered the caspase 3 and 8-mediated apoptosis of tumor cells and downregulated anti-apoptotic Bcl-2 expression upon starvation, which could be further synergized by autophagic inhibitor, indicating that PCBP1 not only inhibits tumor cell autophagy, but also renders them to apoptosis. Taken together, our results uncovered a novel mechanism of PCBP1 in repressing autophagy-mediated cell survival and indicated that inhibition of tumor cell autophagy by PCBP1 upregulation or with autophagic inhibitors could be an effective therapeutical strategy to colon and ovary tumors with low PCBP1 expression.