title: Poly C binding protein 1 represses autophagy through downregulation of LC3B to promote tumor cell apoptosis in starvation.
abstract: 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.
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China; Translational Medicine Centre, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Hongshun
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Hepatic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mao
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tong
authors.affiliation: Department of Internal Medicine, Jinxian People's Hospital of Nanchang, Nanchang, CPZN 331700, People's Republic of China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Translational Medicine Centre, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China. Electronic address: yangshl3@mail.sysu.edu.cn.
authors.forename: Shulan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China; Center for Stem Cell Biology and Tissue Engineering, Sun Yat-sen University, Guangzhou, CPZN 510080, People's Republic of China. Electronic address: wanghaih@mail.sysu.edu.cn.
authors.forename: Haihe
authors.initials: H
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C094604:PCBP1 protein, human; D016601:RNA-Binding Proteins
keywords: Apoptosis; Autophagy; Cancer; LC3B; PCBP1