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

• Published in: The international journal of biochemistry & cell biology 2016-04, Vol.73, p.127-136
• Main Authors: Zhang, Wenliang, Shi, Hongshun, Zhang, Mingming, Liu, Bin, Mao, Shuai, Li, Li, Tong, Fang, Liu, Guoliang, Yang, Shulan, Wang, Haihe
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Attenuation; Autophagy; Autophagy - genetics; Autophagy - physiology; Binding; Cancer; Cell Line, Tumor; Flow Cytometry; Flux; Heterogeneous-Nuclear Ribonucleoproteins - genetics; Heterogeneous-Nuclear Ribonucleoproteins - metabolism; Humans; Inhibition; Inhibitors; LC3B; Microscopy, Fluorescence; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; PCBP1; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tumors
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2016.02.009

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.