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

doi:10.3390/cancers13081772

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

21 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 Kras^G12D-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 language	English
Article number	1772
Journal	Cancers
Volume	13
Issue number	8
DOIs	https://doi.org/10.3390/cancers13081772
State	Published - 2 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

EMT
ID1
Lung cancer
Metastasis
PGC1α
TCF4
TWIST1

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title = "Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition",

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.",

keywords = "EMT, ID1, Lung cancer, Metastasis, PGC1α, TCF4, TWIST1",

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

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = apr,

day = "2",

doi = "10.3390/cancers13081772",

language = "English",

volume = "13",

journal = "Cancers",

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T1 - Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition

AU - Oh, Taek In

AU - Lee, Mingyu

AU - Lee, Yoon Mi

AU - Kim, Geon Hee

AU - Lee, Daekee

AU - You, Jueng Soo

AU - Kim, Sun Ha

AU - Choi, Minyoung

AU - Jang, Hyonchol

AU - Park, Yeong Min

AU - Shin, Hyun Woo

AU - Shin, Dong Hoon

AU - Lim, Ji Hong

PY - 2021/4/2

Y1 - 2021/4/2

N2 - 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.

AB - 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.

KW - EMT

KW - ID1

KW - Lung cancer

KW - Metastasis

KW - PGC1α

KW - TCF4

KW - TWIST1

UR - https://www.scopus.com/pages/publications/85103836185

U2 - 10.3390/cancers13081772

DO - 10.3390/cancers13081772

M3 - Article

AN - SCOPUS:85103836185

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 8

M1 - 1772

ER -

Pgc1α loss promotes lung cancer metastasis through epithelial-mesenchymal transition

Abstract

Bibliographical note

Keywords

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