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Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition
- Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition
- Oh T.-I.; Lee M.; Lee Y.-M.; Kim G.-H.; Lee D.; You J.S.; Kim S.H.; Choi M.; Jang H.; Park Y.-M.; Shin H.-W.; Shin D.H.; Lim J.-H.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Cancers vol. 13, no. 8
- EMT; ID1; Lung cancer; Metastasis; PGC1α; TCF4; TWIST1
- MDPI AG
- SCIE; SCOPUS
- Document Type
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- 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.
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