Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages

Dennis Shin Shian Hsu; Hsiao Jung Wang; Shyh Kuan Tai; Chun Hung Chou; Chia Hsin Hsieh; Po Hsien Chiu; Nien Jung Chen; Muh Hwa Yang

doi:10.1016/j.ccell.2014.09.002

Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages

Dennis Shin Shian Hsu, Hsiao Jung Wang, Shyh Kuan Tai, Chun Hung Chou, Chia Hsin Hsieh, Po Hsien Chiu, Nien Jung Chen, Muh Hwa Yang^*

^*Corresponding author for this work

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

147 Scopus citations

Abstract

Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. CBP interacts with Snail and acetylates Snailat lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.

Original language	English
Pages (from-to)	534-548
Number of pages	15
Journal	Cancer Cell
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2014.09.002
State	Published - 13 Oct 2014

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title = "Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages",

abstract = "Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. CBP interacts with Snail and acetylates Snailat lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.",

author = "Hsu, {Dennis Shin Shian} and Wang, {Hsiao Jung} and Tai, {Shyh Kuan} and Chou, {Chun Hung} and Hsieh, {Chia Hsin} and Chiu, {Po Hsien} and Chen, {Nien Jung} and Yang, {Muh Hwa}",

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year = "2014",

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doi = "10.1016/j.ccell.2014.09.002",

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T1 - Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages

AU - Hsu, Dennis Shin Shian

AU - Wang, Hsiao Jung

AU - Tai, Shyh Kuan

AU - Chou, Chun Hung

AU - Hsieh, Chia Hsin

AU - Chiu, Po Hsien

AU - Chen, Nien Jung

AU - Yang, Muh Hwa

PY - 2014/10/13

Y1 - 2014/10/13

N2 - Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. CBP interacts with Snail and acetylates Snailat lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.

AB - Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. CBP interacts with Snail and acetylates Snailat lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.

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SP - 534

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JO - Cancer Cell

JF - Cancer Cell

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ER -

Acetylation of snail modulates the cytokinome of cancer cells to enhance the recruitment of macrophages

Abstract

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