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Published in: Journal of Cancer Research and Clinical Oncology 5/2024

Open Access 01-05-2024 | Colorectal Cancer | Research

LAMP2A regulates cisplatin resistance in colorectal cancer through mediating autophagy

Authors: Zhiliang Shi, Shuting Yang, Chenglong Shen, Jiazhe Shao, Fang Zhou, Haichen Liu, Guoqiang Zhou

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2024

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Abstract

Background

Drug resistance is an important constraint on clinical outcomes in advanced cancers. LAMP2A is a limiting protein in molecular chaperone-mediated autophagy. This study was aimed to explore LAMP2A function in cisplatin (cis-diamminedichloroplatinum, DDP) resistance colorectal cancer (CRC) to seek new ideas for CRC clinical treatment.

Methods

In this study, LAMP2A expression was analyzed by molecular experimental techniques,such as qRT-PCR and western blot. Then, LAMP2A in cells was interfered by cell transfection experiments. Subsequently, the function of LAMP2A on proliferation, migration, invasion, DDP sensitivity, and autophagy of CRC/DDP cells were further investigated by a series of experiments, such as CCK-8, transwell, and western blot.

Results

We revealed that LAMP2A was clearly augmented in DDP-resistant CRC and was related to poor patient prognosis. Functionally, LAMP2A insertion remarkably CRC/DDP proliferation, migration, invasion ability and DDP resistance by strengthen autophagy. In contrast, LAMP2A knockdown limited the proliferation, migration, and invasion while heightened cellular sensitivity to DDP by restraining autophagy in CRC/DDP cells. Furthermore, LAMP2A silencing was able to curb tumor formation and enhance sensitivity to DDP in vivo.

Conclusion

In summary, LAMP2A boosted malignant progression and DDP resistance in CRC/DDP cells through mediating autophagy. Clarifying LAMP2A function in DDP resistance is promising to seek cancer therapies biomarkers targeting LAMP2A activity.
Literature
go back to reference Ichikawa A, Fujita Y, Hosaka Y, Kadota T, Ito A, Yagishita S, Watanabe N, Fujimoto S, Kawamoto H, Saito N, Yoshida M, Hashimoto M, Minagawa S, Hara H, Motoi N, Yamamoto Y, Ochiya T, Araya J, Kuwano K (2020) Chaperone-mediated autophagy receptor modulates tumor growth and chemoresistance in non-small cell lung cancer. Cancer Sci 111:4154–4165. https://doi.org/10.1111/cas.14629CrossRefPubMedPubMedCentral Ichikawa A, Fujita Y, Hosaka Y, Kadota T, Ito A, Yagishita S, Watanabe N, Fujimoto S, Kawamoto H, Saito N, Yoshida M, Hashimoto M, Minagawa S, Hara H, Motoi N, Yamamoto Y, Ochiya T, Araya J, Kuwano K (2020) Chaperone-mediated autophagy receptor modulates tumor growth and chemoresistance in non-small cell lung cancer. Cancer Sci 111:4154–4165. https://​doi.​org/​10.​1111/​cas.​14629CrossRefPubMedPubMedCentral
Metadata
Title
LAMP2A regulates cisplatin resistance in colorectal cancer through mediating autophagy
Authors
Zhiliang Shi
Shuting Yang
Chenglong Shen
Jiazhe Shao
Fang Zhou
Haichen Liu
Guoqiang Zhou
Publication date
01-05-2024
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 5/2024
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-024-05775-6

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