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Inhibition of chaperone-mediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer
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Inhibition of chaperone-mediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer
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Journal Article
Inhibition of chaperone-mediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer
2021
Overview
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.
Publisher
D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
Subject
/ Cell Proliferation - drug effects
/ chaperone-mediated autophagy
/ Chaperone-Mediated Autophagy - drug effects
/ Chaperone-Mediated Autophagy - genetics
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - pathology
/ Complications and side effects
/ Drug Resistance, Neoplasm - drug effects
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Lysosomal-Associated Membrane Protein 2 - genetics
/ lysosome-associated membrane protein 2A
/ Plasmids
/ Proteins
