H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis

Pei Chun Wu, Jeng Wei Lu, Jer Yen Yang, I. Hsuan Lin, Da Liang Ou, Yu Hsiang Lin, Kuan Hsien Chou, Wen Feng Huang, Wan Ping Wang, Yih Leh Huang, Chiun Hsu, Liang In Lin, Yueh Min Lin, C. K. James Shen, Tsai Yu Tzeng

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis.

Original languageEnglish
Pages (from-to)7333-7343
Number of pages11
JournalCancer Research
Volume74
Issue number24
DOIs
Publication statusPublished - Dec 15 2014
Externally publishedYes

Fingerprint

Lung Neoplasms
Neoplasm Metastasis
Pseudopodia
Tumor Suppressor Genes
Oncogenes
Epigenomics
Histones
Methylation
Neoplasms
Down-Regulation
histone methyltransferase
In Vitro Techniques

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wu, P. C., Lu, J. W., Yang, J. Y., Lin, I. H., Ou, D. L., Lin, Y. H., ... Tzeng, T. Y. (2014). H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. Cancer Research, 74(24), 7333-7343. https://doi.org/10.1158/0008-5472.CAN-13-3572

H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. / Wu, Pei Chun; Lu, Jeng Wei; Yang, Jer Yen; Lin, I. Hsuan; Ou, Da Liang; Lin, Yu Hsiang; Chou, Kuan Hsien; Huang, Wen Feng; Wang, Wan Ping; Huang, Yih Leh; Hsu, Chiun; Lin, Liang In; Lin, Yueh Min; James Shen, C. K.; Tzeng, Tsai Yu.

In: Cancer Research, Vol. 74, No. 24, 15.12.2014, p. 7333-7343.

Research output: Contribution to journalArticle

Wu, PC, Lu, JW, Yang, JY, Lin, IH, Ou, DL, Lin, YH, Chou, KH, Huang, WF, Wang, WP, Huang, YL, Hsu, C, Lin, LI, Lin, YM, James Shen, CK & Tzeng, TY 2014, 'H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis', Cancer Research, vol. 74, no. 24, pp. 7333-7343. https://doi.org/10.1158/0008-5472.CAN-13-3572
Wu, Pei Chun ; Lu, Jeng Wei ; Yang, Jer Yen ; Lin, I. Hsuan ; Ou, Da Liang ; Lin, Yu Hsiang ; Chou, Kuan Hsien ; Huang, Wen Feng ; Wang, Wan Ping ; Huang, Yih Leh ; Hsu, Chiun ; Lin, Liang In ; Lin, Yueh Min ; James Shen, C. K. ; Tzeng, Tsai Yu. / H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. In: Cancer Research. 2014 ; Vol. 74, No. 24. pp. 7333-7343.
@article{b67b7ffef0b14375b20eee1ffe7a4534,
title = "H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis",
abstract = "Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis.",
author = "Wu, {Pei Chun} and Lu, {Jeng Wei} and Yang, {Jer Yen} and Lin, {I. Hsuan} and Ou, {Da Liang} and Lin, {Yu Hsiang} and Chou, {Kuan Hsien} and Huang, {Wen Feng} and Wang, {Wan Ping} and Huang, {Yih Leh} and Chiun Hsu and Lin, {Liang In} and Lin, {Yueh Min} and {James Shen}, {C. K.} and Tzeng, {Tsai Yu}",
year = "2014",
month = "12",
day = "15",
doi = "10.1158/0008-5472.CAN-13-3572",
language = "English",
volume = "74",
pages = "7333--7343",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "24",

}

TY - JOUR

T1 - H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis

AU - Wu, Pei Chun

AU - Lu, Jeng Wei

AU - Yang, Jer Yen

AU - Lin, I. Hsuan

AU - Ou, Da Liang

AU - Lin, Yu Hsiang

AU - Chou, Kuan Hsien

AU - Huang, Wen Feng

AU - Wang, Wan Ping

AU - Huang, Yih Leh

AU - Hsu, Chiun

AU - Lin, Liang In

AU - Lin, Yueh Min

AU - James Shen, C. K.

AU - Tzeng, Tsai Yu

PY - 2014/12/15

Y1 - 2014/12/15

N2 - Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis.

AB - Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis.

UR - http://www.scopus.com/inward/record.url?scp=84918513875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918513875&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-13-3572

DO - 10.1158/0008-5472.CAN-13-3572

M3 - Article

C2 - 25477335

AN - SCOPUS:84918513875

VL - 74

SP - 7333

EP - 7343

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 24

ER -