A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer

X. Zhang; L. Zhang; Y. Du; H. Zheng; P. Zhang; Y. Sun; Y. Wang; J. Chen; P. Ding; N. Wang; C. Yang; T. Huang; X. Yao; Q. Qiao; H. Gu; G. Cai; S. Cai; X. Zhou; W. Hu

doi:10.1038/onc.2016.249

A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer

X. Zhang, L. Zhang, Y. Du, H. Zheng, P. Zhang, Y. Sun, Y. Wang, J. Chen, P. Ding, N. Wang, C. Yang, T. Huang, X. Yao, Q. Qiao, H. Gu, G. Cai, S. Cai, X. Zhou, W. Hu

Cancer Biology

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

46 Scopus citations

Abstract

Epithelial-mesenchymal transition (EMT) is a critical event in metastasis of colorectal cancer (CRC). Rho/ROCKs signaling has a pivotal role in orchestrating actin cytoskeleton, leading to EMT and cancer invasion. However, the underlying mechanisms for ROCKs activation are not fully understood. Here, we identified FOXM1D, a novel isoform of Forkhead box M1 (FOXM1) that has a pivotal role in ROCKs activation by directly interacting with coiled-coil region of ROCK2. FOXM1D overexpression significantly polymerizes actin assembly and impairs E-cadherin expression, resulting in EMT and metastasis in xenograft mouse model and knockdown of FOXM1D has the opposite effect. Moreover, a high FOXM1D level correlates closely with clinical CRC metastasis. FOXM1D-induced ROCKs activation could be abrogated by the ROCKs inhibitors Y-27632 and fasudil. These observations indicate that the FOXM1D-ROCK2 interaction is crucial for Rho/ROCKs signaling and provide novel insight into actin cytoskeleton regulation and therapeutic potential for CRC metastasis.

Original language	English (US)
Pages (from-to)	807-819
Number of pages	13
Journal	Oncogene
Volume	36
Issue number	6
DOIs	https://doi.org/10.1038/onc.2016.249
State	Published - Feb 9 2017

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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Zhang, X., Zhang, L., Du, Y., Zheng, H., Zhang, P., Sun, Y., Wang, Y., Chen, J., Ding, P., Wang, N., Yang, C., Huang, T., Yao, X., Qiao, Q., Gu, H., Cai, G., Cai, S., Zhou, X., & Hu, W. (2017). A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. Oncogene, 36(6), 807-819. https://doi.org/10.1038/onc.2016.249

Zhang, X, Zhang, L, Du, Y, Zheng, H, Zhang, P, Sun, Y, Wang, Y, Chen, J, Ding, P, Wang, N, Yang, C, Huang, T, Yao, X, Qiao, Q, Gu, H, Cai, G, Cai, S, Zhou, X & Hu, W 2017, 'A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer', Oncogene, vol. 36, no. 6, pp. 807-819. https://doi.org/10.1038/onc.2016.249

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title = "A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer",

abstract = "Epithelial-mesenchymal transition (EMT) is a critical event in metastasis of colorectal cancer (CRC). Rho/ROCKs signaling has a pivotal role in orchestrating actin cytoskeleton, leading to EMT and cancer invasion. However, the underlying mechanisms for ROCKs activation are not fully understood. Here, we identified FOXM1D, a novel isoform of Forkhead box M1 (FOXM1) that has a pivotal role in ROCKs activation by directly interacting with coiled-coil region of ROCK2. FOXM1D overexpression significantly polymerizes actin assembly and impairs E-cadherin expression, resulting in EMT and metastasis in xenograft mouse model and knockdown of FOXM1D has the opposite effect. Moreover, a high FOXM1D level correlates closely with clinical CRC metastasis. FOXM1D-induced ROCKs activation could be abrogated by the ROCKs inhibitors Y-27632 and fasudil. These observations indicate that the FOXM1D-ROCK2 interaction is crucial for Rho/ROCKs signaling and provide novel insight into actin cytoskeleton regulation and therapeutic potential for CRC metastasis.",

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AU - Huang, T.

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AU - Qiao, Q.

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A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer

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