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Microtubule-associated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma

Oncogene volume 35, pages 4846–4856 (2016)Cite this article

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Abstract

Cell invasion and migration significantly contribute to tumor metastasis. Microtubule-associated protein 4 (MAP4) protein is one member of microtubule-associate proteins family. It is responsible for stabilization of microtubules by modulation of microtubule dynamics. However, there is little information about the involvement of MAP4 in human cancer. Here we show that MAP4 serves as a regulator of invasion and migration in esophageal squamous cancer cells. By activating the ERK-c-Jun-vascular endothelial growth factor A signaling pathway, MAP4 promotes cell invasion and migration in vitro, tumor growth and metastasis in mouse models. Immunohistochemical staining of operative tissues indicated that MAP4 expression was associated with tumor stage, lymph node metastasis and shorter survival of the patients with esophageal squamous cell carcinoma (ESCC). Multivariate Cox regression analysis showed that MAP4 is an independent prognostic indicator. In the serial sections of ESCC tissues, there was a positive correlation between MAP4 and vascular endothelial growth factor A expression. Notably, an intratumoral injection of MAP4-small interfering RNA (siRNA) remarkably inhibited the growth of the tumors that formed by the MAP4-expressing ESCC cells in nude mice, and a combination of MAP4-siRNA and Bevacizumab significantly enhanced the inhibition effect. Our data suggest that MAP4 is probably a useful prognostic biomarker and a potential therapeutic target for the disease.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (81330052 and 81321091) and National High-Tech R&D Program of China (2012AA02A503 and 2012AA020206).

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Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

    Y-Y Jiang, L Shang, Z-Z Shi, T-T Zhang, S Ma, Y Zhang, J-J Hao, C Shi, F Shi, X Xu, Y Cai, Q–M Zhan & M-R Wang

  2. Department of Histology and Embryology, Anhui Medical University, Hefei, China

    C-C Lu & X-M Jia

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Jiang, YY., Shang, L., Shi, ZZ. et al. Microtubule-associated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma. Oncogene 35, 4846–4856 (2016). https://doi.org/10.1038/onc.2016.17

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