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RETRACTED ARTICLE: FOXC2 promotes colorectal cancer metastasis by directly targeting MET

Oncogene volume 34, pages 4379–4390 (2015)Cite this article

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A Retraction to this article was published on 01 April 2022

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Abstract

Metastasis is the major cause of death in colorectal cancer (CRC). Although multiple genes have been identified to be responsible for the development of CRC, the molecular changes that enable CRC cells to undergo early local invasion and to form distant metastatic colonies still remain largely unknown. Herein, we investigated the role of Forkhead box protein C2 (FOXC2) and explored the underlying mechanisms in invasion and metastasis of CRC. We show that both high FOXC2 expression and nuclear localization of FOXC2 are significantly correlated with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis) stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted local invasion and distant metastasis in an orthotopic mouse metastatic model of CRC. Microarray analysis revealed that overexpression of FOXC2 increased the proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and chromatin immunoprecipitation assays revealed that FOXC2 directly associated with MET promoter to increase the transcriptional activity of MET. Inhibition of MET attenuates the invasive phenotype and metastatic potential of FOXC2-overexpressing CRC cells, indicating that MET is a major mediator of FOXC2-promoted metastasis. In addition, FOXC2 expression was positively correlated with MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET expression, highlighting FOXC2 as a potential therapeutic target for preventing or reducing metastasis in CRC.

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Acknowledgements

This work was supported by the National Basic Research Program of China (973 program, nos. 2015CB554002 and 2010CB529403), the National Natural Science Foundation of China (NSFC)-Guangdong Joint Fund (U1201226), the Major Projects of the National Natural Science Foundation of China (no. 81090422), the National Natural Science Foundation of China (nos. 30901791, 81172055, 81472313, 81472710 and 81071735), Guangdong Provincial Natural Science Foundation of China (no. S2012010009643), Zhu Jiang Science & Technology New Star Foundation in Guangzhou city (2012J2200052 and 2012J2200044), the Science and Technology Innovation Foundation of Guangdong Higher Education (CXZD1016), the Key Program of the National Natural Science Foundation of Guangdong, China (2010B031500012), and Guangzhou Science & Technology Plan Project (201300000056).

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Author notes

  1. Y-M Cui and H-L Jiao: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Y-M Cui, H-L Jiao, Y-P Ye, C-M Chen, J-X Wang, N Tang, T-T Li, J Lin, L Qi, P Wu, S-Y Wang, L Liang, W-T Liao & Y-Q Ding

  2. Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

    Y-M Cui, H-L Jiao, Y-P Ye, C-M Chen, J-X Wang, N Tang, T-T Li, J Lin, L Qi, P Wu, S-Y Wang, L Liang, W-T Liao & Y-Q Ding

  3. Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, China

    Y-M Cui, H-L Jiao, Y-P Ye, C-M Chen, J-X Wang, N Tang, T-T Li, J Lin, L Qi, P Wu, S-Y Wang, L Liang, W-T Liao & Y-Q Ding

  4. Guangdong Provincial Key Laboratory of Gastroenterology and Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    M-R He

  5. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China

    X-W Bian

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Correspondence to W-T Liao or Y-Q Ding.

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Supplementary Information accompanies this paper on the Oncogene website

This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1038/s41388-022-02287-w

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Cui, YM., Jiao, HL., Ye, YP. et al. RETRACTED ARTICLE: FOXC2 promotes colorectal cancer metastasis by directly targeting MET. Oncogene 34, 4379–4390 (2015). https://doi.org/10.1038/onc.2014.368

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  • DOI: https://doi.org/10.1038/onc.2014.368

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