Inhibition of chaperone‑mediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer
- Ying Xuan
- Shuang Zhao
- Xingjun Xiao
- Liwei Xiang
- Hua-Chuan Zheng
Affiliations: Department of Experimental Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
- Published online on: March 12, 2021 https://doi.org/10.3892/mmr.2021.11999
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Chaperone‑mediated autophagy (CMA) is a selective type of autophagy whereby a specific subset of intracellular proteins is targeted to the lysosome for degradation. The present study investigated the mechanisms underlying the response and resistance to 5‑fluorouracil (5‑FU) in colorectal cancer (CRC) cell lines. In engineered 5‑FU‑resistant CRC cell lines, a significant elevation of lysosome‑associated membrane protein 2A (LAMP2A), which is the key molecule in the CMA pathway, was identiﬁed. High expression of LAMP2A was found to be responsible for 5‑FU resistance and to enhance PLD2 expression through the activation of NF‑κB pathway. Accordingly, loss or gain of function of LAMP2A in 5‑FU‑resistant CRC cells rendered them sensitive or resistant to 5‑FU, respectively. Taken together, the results of the present study suggested that chemoresistance in patients with CRC may be mediated by enhancing CMA. Thus, CMA is a promising predictor of chemosensitivity to 5‑FU treatment and anti‑CMA therapy may be a novel therapeutic option for patients with CRC.