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

被引：40

作者：

Jiang, Y-Y ^{[1
,2
]}

Shang, L. ^{[1
,2
]}

Shi, Z-Z ^{[1
,2
]}

Zhang, T-T ^{[1
,2
]}

Ma, S. ^{[1
,2
]}

Lu, C-C ^{[3
]}

Zhang, Y. ^{[1
,2
]}

Hao, J-J ^{[1
,2
]}

Shi, C. ^{[1
,2
]}

Shi, F. ^{[1
,2
]}

Xu, X. ^{[1
,2
]}

Cai, Y. ^{[1
,2
]}

Jia, X-M ^{[3
]}

Zhan, Q-M ^{[1
,2
]}

Wang, M-R ^{[1
,2
]}

机构：

[1] Peking Union Med Coll, Canc Inst Hosp, State Key Lab Mol Oncol, Panjiayuan South 17, Beijing 100021, Peoples R China

[2] Chinese Acad Med Sci, Panjiayuan South 17, Beijing 100021, Peoples R China

[3] Anhui Med Univ, Dept Histol & Embryol, Hefei, Peoples R China

来源：

ONCOGENE | 2016年 / 35卷 / 37期

基金：

中国国家自然科学基金;

关键词：

ENDOTHELIAL GROWTH-FACTOR; CANCER CELLS; BREAST-CANCER; TUMOR-GROWTH; FACTOR VEGF; P38; MAPK; ANGIOGENESIS; INVASION; PATHWAY; METASTASIS;

D O I：

10.1038/onc.2016.17

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4846 / 4856

页数：11

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