Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition

Taek In Oh, Mingyu Lee, Yoon Mi Lee, Geon Hee Kim, Daekee Lee, Jueng Soo You, Sun Ha Kim, Minyoung Choi, Hyonchol Jang, Yeong Min Park, Hyun Woo Shin, Dong Hoon Shin, Ji Hong Lim

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial–mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of KrasG12D-driven lung cancer. Mechanistically, PGC1α predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1α and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1α-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer.

Original languageEnglish
Article number1772
JournalCancers
Volume13
Issue number8
DOIs
StatePublished - 2 Apr 2021

Keywords

  • EMT
  • ID1
  • Lung cancer
  • Metastasis
  • PGC1α
  • TCF4
  • TWIST1

Fingerprint

Dive into the research topics of 'Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition'. Together they form a unique fingerprint.

Cite this