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

  • Oncogene. 2023 Jul 3. doi: 10.1038/s41388-023-02762-y.
Wei Chen  #  1 ,  Qiushuang Zhang  #  1 ,  Xiaoshuo Dai  1 ,  Xinhuan Chen  1  2  3 ,  Chengjuan Zhang  4 ,  Ruihua Bai  4 ,  Yihuan Chen  1 ,  Kai Zhang  1 ,  Xiaoxuan Duan  1 ,  Yan Qiao  1  2  3 ,  Jimin Zhao  1  2  3 ,  Fang Tian  1  2  3 ,  Kangdong Liu  1  2  3 ,  Ziming Dong  1  2  3 ,  Jing Lu  5  6  7
Affiliations
  • 1. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, P. R. China.
  • 2. Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan Province, 450001, P. R. China.
  • 3. State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, P. R. China.
  • 4. Department of Pathology, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, Henan Province, 450003, P. R. China.
  • 5. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, P. R. China. [email protected].
  • 6. Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan Province, 450001, P. R. China. [email protected].
  • 7. State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, P. R. China. [email protected].
  • # Contributed equally.
PMID: 37400530 DOI: 10.1038/s41388-023-02762-y
Abstract

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.

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