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, Min-Young Choi, Hyonchol Jang, Yeong-Min Park, Hyun‐Woo Shin, Dong Hoon Shin, Ji‐Hong Lim
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.