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.

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“…HnRNP E1 has been proven to promote cell apoptosis in several cancer cell lines [20][21][22]. Recently, a research group reported that hnRNP E1 repressed autophagy through downregulation of LC3B to promote tumor cell apoptosis [23]. In endothelial cells, hnRNP E1 serves as a key protective mechanism through increasing human endothelial nitric oxide synthase (eNOS) mRNA stability and we found hnRNP E1 is a new regulator of endothelium-protein disulphide isomerase translation in oxLDL-activated VECs [24,25].…”

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“…The other paper suggested that PCBP1 was responsible for stabilizing gastrin mRNA which was highly expressed in colorectal adenocarcinoma (38). PCBP1 represses autophagymediated cell survival and inhibition of tumor cell autophagy and the PCBP1 upregulation may be an effective therapeutic strategy to colon tumor with low PCBP1 expression (39). LIFR(p=4.90e-04) had 4 hit papers and encodes protein that belongs to the type I cytokine receptor family.…”