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

doi:10.1158/0008-5472.CAN-13-3572

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 journal › Article › peer-review

60 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 language	English
Pages (from-to)	7333-7343
Number of pages	11
Journal	Cancer Research
Volume	74
Issue number	24
DOIs	https://doi.org/10.1158/0008-5472.CAN-13-3572
Publication status	Published - Dec 15 2014
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/0008-5472.CAN-13-3572

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Wu, P. C., Lu, J. W., Yang, J. Y., Lin, I. H., Ou, D. L., Lin, Y. H., Chou, K. H., Huang, W. F., Wang, W. P., Huang, Y. L., Hsu, C., Lin, L. I., Lin, Y. M., James Shen, C. K., & 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

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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}",

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doi = "10.1158/0008-5472.CAN-13-3572",

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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.

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

Abstract

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UN SDGs

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