Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition
- 주제(키워드) EMT , ID1 , Lung cancer , Metastasis , PGC1α , TCF4 , TWIST1
- 후원정보 Shin, H.-W.; Obstructive Upper airway Research (OUaR) Laboratory, South Korea; email: charlie@snu.ac.kr Shin, H.-W.; Department of Biomedical Sciences, South Korea; email: charlie@snu.ac.kr Shin, H.-W.; Cancer Research Institute, South Korea; email: charlie@snu.ac.kr Shin, D.H.; Research Institute, South Korea; email: dhshin@ncc.re.kr Lim, J.-H.; Department of Biomedical Chemistry, South Korea; email: jhlim@kku.ac.kr Lim, J.-H.; Department of Applied Life Science, South Korea; email: jhlim@kku.ac.kr Lim, J.-H.; Diabetes and Bio-Research Center, South Korea; email: jhlim@kku.ac.kr
- 등재 SCIE, SCOPUS
- 발행기관 MDPI AG
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000181823
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/cancers13081772
초록/요약
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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
more