Chaperon‑mediated autophagy can promote proliferation and invasion of renal carcinoma cells and inhibit apoptosis through PKM2

Xiao,Shangwen; Xu,Gang; Wang,Zhenlong; Chong,Tie

doi:10.3892/or.2021.8165

Chaperon‑mediated autophagy can promote proliferation and invasion of renal carcinoma cells and inhibit apoptosis through PKM2

Authors:
- Shangwen Xiao
- Gang Xu
- Zhenlong Wang
- Tie Chong
View Affiliations

Affiliations: Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, Ankang Hospital of Traditional Chinese Medicine, Ankang, Shaanxi 72500, P.R. China, Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: August 3, 2021 https://doi.org/10.3892/or.2021.8165
Article Number: 214

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to explore the effect of chaperon‑mediated autophagy (CMA) through pyruvate kinase isoform M2 (PKM2) on the development of renal carcinoma (RCC) and its possible mechanisms. Lysosome‑associated membrane protein 2A (LAMP‑2A) and PKM2 expression levels were detected by collecting tissue samples from RCC patients. RNA interference was used to silence the LAMP‑2A and PKM2 expression levels in renal cell line A498 to detect the proliferation, apoptosis and invasion of cells. The levels of mRNA and protein of related genes were also examined. Co‑immunoprecipitation was used to detect the interaction between PKM2 and heat shock cognate 70 (HSC70). The results revealed that LAMP‑2A and PKM2 expression levels were significantly increased in RCC tissues and cell lines (P<0.01). LAMP‑2A silencing increased the expression level of PKM2 in A498 and 786‑O cells. LAMP‑2A and PKM2 silencing suppressed the proliferation and invasion and induced the apoptosis of A498 cells, and also affected the expression levels of related genes. Co‑immunoprecipitation revealed the interaction between PKM2 and HSC70. In conclusion, CMA could affect the proliferation, invasion and apoptosis of RCC cells through PKM2, and our findings provided new biomarkers and targets for molecular targeted therapy of RCC.

View Figures

View References

1	Cuervo AM: Chaperone-mediated autophagy: Selectivity pays off. Trends Endocrinol Metab. 21:142–150. 2010. View Article : Google Scholar : PubMed/NCBI
2	Agarraberes FA, Terlecky SR and Dice JF: An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol. 137:825–834. 1997. View Article : Google Scholar : PubMed/NCBI
3	Park C, Suh Y and Cuervo AM: Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Nat Commun. 6:68232015. View Article : Google Scholar : PubMed/NCBI
4	Saha T: LAMP2A overexpression in breast tumors promotes cancer cell survival via chaperone-mediated autophagy. Autophagy. 8:1643–1656. 2012. View Article : Google Scholar : PubMed/NCBI
5	Kon M, Kiffin R, Koga H, Chapochnick J, Macian F, Varticovski L and Cuervo AM: Chaperone-mediated autophagy is required for tumor growth. Sci Transl Med. 3:109ra1172011. View Article : Google Scholar : PubMed/NCBI
6	Zhou J, Yang J, Fan X, Hu S, Zhou F, Dong J, Zhang S, Shang Y, Jiang X, Guo H, et al: Chaperone-mediated autophagy regulates proliferation by targeting RND3 in gastric cancer. Autophagy. 12:515–528. 2016. View Article : Google Scholar : PubMed/NCBI
7	Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI
8	Altenberg B and Greulich KO: Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics. 84:1014–1020. 2004. View Article : Google Scholar : PubMed/NCBI
9	Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, et al: mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 10:594–601. 2004. View Article : Google Scholar : PubMed/NCBI
10	Mazurek S, Boschek CB, Hugo F and Eigenbrodt E: Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol. 15:300–308. 2005. View Article : Google Scholar : PubMed/NCBI
11	Dombrauckas JD, Santarsiero BD and Mesecar AD: Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry. 44:9417–9429. 2005. View Article : Google Scholar : PubMed/NCBI
12	Li YH, Li XF, Liu JT, Wang H, Fan LL, Li J and Sun GP: PKM2, a potential target for regulating cancer. Gene. 668:48–53. 2018. View Article : Google Scholar : PubMed/NCBI
13	Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, et al: Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell. 42:719–730. 2011. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Zhang S, Hu B, You Y, Yang Z, Liu L, Tang H, Bao W, Guan Y and Shen X: Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of colorectal cancer through regulating chaperone mediated autophagy degradation of p21^Cip1/WAF1. Cancer Lett. 419:116–127. 2018. View Article : Google Scholar : PubMed/NCBI
16	Arias E and Cuervo AM: Pros and cons of chaperone-mediated autophagy in cancer biology. Trends Endocrinol Metab. 31:53–66. 2020. View Article : Google Scholar : PubMed/NCBI
17	Zhang Z, Deng X, Liu Y, Liu Y, Sun L and Chen F: PKM2, function and expression and regulation. Cell Biosci. 9:522019. View Article : Google Scholar : PubMed/NCBI
18	Zhang J, Feng G, Bao G, Xu G, Sun Y, Li W, Wang L, Chen J, Jin H and Cui Z: Nuclear translocation of PKM2 modulates astrocyte proliferation via p27 and -catenin pathway after spinal cord injury. Cell Cycle. 14:2609–2618. 2015. View Article : Google Scholar : PubMed/NCBI
19	Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, Simmet T and Seufferlein T: PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 15:32016. View Article : Google Scholar : PubMed/NCBI
20	de Wit RH, Mujić-Delić A, van Senten JR, Fraile-Ramos A, Siderius M and Smit MJ: Human cytomegalovirus encoded chemokine receptor US28 activates the HIF-1α/PKM2 axis in glioblastoma cells. Oncotarget. 7:67966–67985. 2016. View Article : Google Scholar : PubMed/NCBI
21	Peng JQ, Han SM, Chen ZH, Yang J, Pei YQ, Bao C, Qiao L, Chen WQ and Liu B: Chaperone-mediated autophagy regulates apoptosis and the proliferation of colon carcinoma cells. Biochem Biophys Res Commun. 522:348–354. 2020. View Article : Google Scholar : PubMed/NCBI
22	Liang J, Cao R, Wang X, Zhang Y, Wang P, Gao H, Li C, Yang F, Zeng R, Wei P, et al: Mitochondrial PKM2 regulates oxidative stress-induced apoptosis by stabilizing Bcl2. Cell Res. 27:329–351. 2017. View Article : Google Scholar : PubMed/NCBI
23	Lu WQ, Hu YY, Lin XP and Fan W: Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells. Oncotarget. 8:44171–44185. 2017. View Article : Google Scholar : PubMed/NCBI
24	Yuan S, Qiao T, Zhuang X, Chen W, Xing N and Zhang Q: Knockdown of the M2 isoform of pyruvate kinase (PKM2) with shRNA enhances the effect of docetaxel in human NSCLC cell lines in vitro. Yonsei Med J. 57:1312–1323. 2016. View Article : Google Scholar : PubMed/NCBI
25	Gorantla NV and Chinnathambi S: Autophagic pathways to clear the tau aggregates in Alzheimer's disease. Cell Mol Neurobiol. 41:1175–1181. 2021. View Article : Google Scholar : PubMed/NCBI