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

18 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.",

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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}",

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day = "2",

doi = "10.3390/cancers13081772",

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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

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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

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KW - TWIST1

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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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