PGC-1α promotes colorectal carcinoma metastasis through regulating ABCA1 transcription.

Colorectal cancer (CRC) is a highly aggressive cancer in which metastasis plays a key role. However, the mechanisms underlying metastasis have not been fully elucidated. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a regulator of mitochondrial function, has been reported as a complicated factor in cancer. In this study, we found that PGC-1α was highly expressed in CRC tissues and was positively correlated with lymph node and liver metastasis. Subsequently, PGC-1α knockdown was shown to inhibit CRC growth and metastasis in both in vitro and in vivo studies. Transcriptomic analysis revealed that PGC-1α regulated ATP-binding cassette transporter 1 (ABCA1) mediated cholesterol efflux. Mechanistically, PGC-1α interacted with YY1 to promote ABCA1 transcription, resulting in cholesterol efflux, which subsequently promoted CRC metastasis through epithelial-to-mesenchymal transition (EMT). In addition, the study identified the natural compound isoliquiritigenin (ISL) as an inhibitor that targeted ABCA1 and significantly reduced CRC metastasis induced by PGC-1α. Overall, this study sheds light on how PGC-1α promotes CRC metastasis by regulating ABCA1-mediated cholesterol efflux, providing a basis for further research to inhibit CRC metastasis. © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Wei Chen, Qiushuang Zhang, Xiaoshuo Dai, Xinhuan Chen, Chengjuan Zhang, Ruihua Bai, Yihuan Chen, Kai Zhang, Xiaoxuan Duan, Yan Qiao, Jimin Zhao, Fang Tian, Kangdong Liu, Ziming Dong, Jing Lu. PGC-1α promotes colorectal carcinoma metastasis through regulating ABCA1 transcription. Oncogene. 2023 Aug;42(32):2456-2470

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PMID: 37400530

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