LAMP2A overexpression in colorectal cancer promotes cell growth and glycolysis via chaperone‑mediated autophagy

Chen,Rui; Zhang,Yanfei; Ge,Yuanxun; He,Chao; Wu,Zongyao; Wang,Junhua; Yu,Jin; Xiao,Jing; Zhang,Xu; Tao,Minghua; Wang,Zi; Pan,Li; He,Meng; Li,Shuhui; Han,Qi

doi:10.3892/ol.2023.14164

LAMP2A overexpression in colorectal cancer promotes cell growth and glycolysis via chaperone‑mediated autophagy

Authors:
- Rui Chen
- Yanfei Zhang
- Yuanxun Ge
- Chao He
- Zongyao Wu
- Junhua Wang
- Jin Yu
- Jing Xiao
- Xu Zhang
- Minghua Tao
- Zi Wang
- Li Pan
- Meng He
- Shuhui Li
- Qi Han
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Affiliations: Institute of Tibetan medicine, University of Tibetan Medicine, Lhasa, Tibet Autonomous Region 850007, P.R. China, Nuclear Medicine Department, General Hospital of Tibet Military Area Command, Lhasa, Tibet Autonomous Region 850000, P.R. China, Clinical Biochemistry Laboratory, Army Medical University (Third Military Medical University), Chongqing 400038, P.R. China
Published online on: November 22, 2023 https://doi.org/10.3892/ol.2023.14164
Article Number: 33
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lysosome‑associated membrane protein type 2A (LAMP2A) is a key protein in the chaperone‑mediated autophagy (CMA) pathway and has been demonstrated to be involved in the pathogenesis of a number of tumors. However, the role of CMA in colorectal cancer cell proliferation, metastasis and cell survival during oxidative stress and oxaliplatin resistance remains to be elucidated. In the present study, elevated expression of LAMP2A was observed in colon cancer tissues. Then, CMA activity was increased in SW480 and HT29 colorectal cancer cells with a LAMP2A overexpression vector and CMA activity was decreased using a LAMP2A short interfering RNA vector. MTT and colony formation assays showed that the colorectal cancer cell proliferation ability and cell viability following treatment with H₂O₂ or oxaliplatin were decreased significantly after LAMP2A knockdown and increased significantly after LAMP2A overexpression. Wound healing assays and Transwell invasion assays demonstrated that downregulation of LAMP2A expression inhibited the cell migration and invasion abilities of colorectal cancer and that upregulation of LAMP2A expression promoted cell migration and invasion. Extracellular acidification rate (ECAR) assay and lactate determination assay showed that glycolysis in colorectal cancer cells was significantly downregulated after LAMP2A knockdown and significantly upregulated after LAMP2A overexpression. Inhibition of glycolysis by 2‑DG markedly attenuated LAMP2A‑induced chemoresistance in colorectal cancer cells. Collectively, these data indicated that CMA can promote colorectal cancer cell proliferation, metastasis and cell survival during oxidative stress and oxaliplatin resistance and that the mechanism is related to the glycolytic pathway, which may provide a new therapeutic target for colorectal cancer patients.

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