Metastasis-associated Protein 1 Induces VEGF-C and Facilitates Lymphangiogenesis in Colorectal Cancer
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Aim: To study the correlation between high metastasis-associated protein 1 (MTA1) expression and lymphangiogenesis in colorectal cancer (CRC) and its role in production of vascular endothelial growth factor-C(VEGF-C).
Methods: Impact of high MTA1 and VEGF-C expression levels on disease progression and lymphovascular density (LVD, D2-40-immunolabeled) in 81 cases of human CRC was evaluated by immunohistochemistry. VEGF-C mRNA and protein expressions in human LoVo and HCT116 cell lines were detected by real-time polymerase chain reaction and Western blotting, respectively, with a stable expression vector or siRNA.
Results: The elevated MTA1 and VEGF-C expression levels were correlated with lymph node metastasis and Dukes stages (P < 0.05). Additionally, high MTA1 expression level was correlated with a large tumor size (P < 0.05). A significant correlation was found between MTA1 and VEGF-C protein expressions in tumor cells (r = 0.371, P < 0.05). Similar to the VEGF-C expression level, high MTA1 expression level was correlated with high LVD in CRC (P < 0.05). Furthermore, over-expression of MTA1 significantly enhanced the VEGF-C mRNA and protein expression levels, whereas siRNAs - knocked down MTA1 decreased the VEGF-C expression level.
Conclusion: MTA1, as a regulator of tumor-associated lymphangiogenesis, promotes lymphangiogenesis in CRC by mediating the VEGF-C expression.
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Zhao A, Zhao Y, Feng W, Zhao Z, Liu W, Wang N J Musculoskelet Neuronal Interact. 2022; 22(2):261-268.
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Zhang Y, Liu Y, Shen D, Zhang H, Huang H, Li S Transl Cancer Res. 2022; 9(10):6189-6197.
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PMID: 33409150 PMC: 7780747. DOI: 10.3389/fonc.2020.542330.