Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion

Yadi Wu; Jiong Deng; Piotr G. Rychahou; Suimin Qiu; B. Mark Evers; Binhua P. Zhou

doi:10.1016/j.ccr.2009.03.016

Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion

Yadi Wu, Jiong Deng, Piotr G. Rychahou, Suimin Qiu, B. Mark Evers, Binhua P. Zhou

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

711 Scopus citations

Abstract

The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT), which occurs during embryonic development, wound healing, and metastasis. In this study, we found that Snail is stabilized by the inflammatory cytokine TNFα through the activation of the NF-κB pathway. We demonstrated that NF-κB is required for the induction of COP9 signalosome 2 (CSN2), which, in turn, blocks the ubiquitination and degradation of Snail. Furthermore, we showed that the expression of Snail correlated with the activation of NF-κB in cancer cell lines and metastatic tumor samples. Knockdown of Snail expression inhibited cell migration and invasion induced by inflammatory cytokines and suppressed inflammation-mediated breast cancer metastasis. Our study provides a plausible mechanism for inflammation-induced metastasis.

Original language	English
Pages (from-to)	416-428
Number of pages	13
Journal	Cancer Cell
Volume	15
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2009.03.016
State	Published - May 5 2009

Bibliographical note

Funding Information:
We thank Dr. Warner C. Greene for providing wild-type and deletion mutants of p65. We also thank Dr. James R. Woodgett for providing immortalized wild-type and GSK-3β −/− MEFs. This work was supported by the John Sealy Memorial Endowment Fund, a pilot award from the ACS (IRG-110376), grants from the Susan G. Komen Foundation (KG081310) and NCI (RO1-CA125454) (to B.P.Z.), and grants RO1 CA104748 and RO1 DK48498 from the NIH (to B.M.E.). Y.W. was supported by postdoctoral fellowship from NIH (T32CA117834).

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

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10.1016/j.ccr.2009.03.016

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title = "Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion",

abstract = "The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT), which occurs during embryonic development, wound healing, and metastasis. In this study, we found that Snail is stabilized by the inflammatory cytokine TNFα through the activation of the NF-κB pathway. We demonstrated that NF-κB is required for the induction of COP9 signalosome 2 (CSN2), which, in turn, blocks the ubiquitination and degradation of Snail. Furthermore, we showed that the expression of Snail correlated with the activation of NF-κB in cancer cell lines and metastatic tumor samples. Knockdown of Snail expression inhibited cell migration and invasion induced by inflammatory cytokines and suppressed inflammation-mediated breast cancer metastasis. Our study provides a plausible mechanism for inflammation-induced metastasis.",

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note = "Funding Information: We thank Dr. Warner C. Greene for providing wild-type and deletion mutants of p65. We also thank Dr. James R. Woodgett for providing immortalized wild-type and GSK-3β −/− MEFs. This work was supported by the John Sealy Memorial Endowment Fund, a pilot award from the ACS (IRG-110376), grants from the Susan G. Komen Foundation (KG081310) and NCI (RO1-CA125454) (to B.P.Z.), and grants RO1 CA104748 and RO1 DK48498 from the NIH (to B.M.E.). Y.W. was supported by postdoctoral fellowship from NIH (T32CA117834). ",

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AU - Qiu, Suimin

AU - Evers, B. Mark

AU - Zhou, Binhua P.

N1 - Funding Information: We thank Dr. Warner C. Greene for providing wild-type and deletion mutants of p65. We also thank Dr. James R. Woodgett for providing immortalized wild-type and GSK-3β −/− MEFs. This work was supported by the John Sealy Memorial Endowment Fund, a pilot award from the ACS (IRG-110376), grants from the Susan G. Komen Foundation (KG081310) and NCI (RO1-CA125454) (to B.P.Z.), and grants RO1 CA104748 and RO1 DK48498 from the NIH (to B.M.E.). Y.W. was supported by postdoctoral fellowship from NIH (T32CA117834).

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N2 - The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT), which occurs during embryonic development, wound healing, and metastasis. In this study, we found that Snail is stabilized by the inflammatory cytokine TNFα through the activation of the NF-κB pathway. We demonstrated that NF-κB is required for the induction of COP9 signalosome 2 (CSN2), which, in turn, blocks the ubiquitination and degradation of Snail. Furthermore, we showed that the expression of Snail correlated with the activation of NF-κB in cancer cell lines and metastatic tumor samples. Knockdown of Snail expression inhibited cell migration and invasion induced by inflammatory cytokines and suppressed inflammation-mediated breast cancer metastasis. Our study provides a plausible mechanism for inflammation-induced metastasis.

AB - The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT), which occurs during embryonic development, wound healing, and metastasis. In this study, we found that Snail is stabilized by the inflammatory cytokine TNFα through the activation of the NF-κB pathway. We demonstrated that NF-κB is required for the induction of COP9 signalosome 2 (CSN2), which, in turn, blocks the ubiquitination and degradation of Snail. Furthermore, we showed that the expression of Snail correlated with the activation of NF-κB in cancer cell lines and metastatic tumor samples. Knockdown of Snail expression inhibited cell migration and invasion induced by inflammatory cytokines and suppressed inflammation-mediated breast cancer metastasis. Our study provides a plausible mechanism for inflammation-induced metastasis.

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Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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