Increased expression of GEF-H1 promotes colon cancer progression by RhoA signaling

被引：18
作者：
Cao, Jun [1 ]
Yang, Tian [1 ]
Tang, DeHua [1 ]
Zhou, Fan [1 ]
Qian, YuanXia [2 ]
Zou, XiaoPing [1 ]
机构：
[1] Nanjing Univ, Med Sch, Dept Gastroenterol, Affiliated Hosp,Nanjing Drum Tower Hosp, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China
[2] Zhenjiang Hosp Chinese Tradit & Western Med, Dept Pharm, Zhenjiang 212000, Jiangsu, Peoples R China
来源：
PATHOLOGY RESEARCH AND PRACTICE | 2019年 / 215卷 / 05期
关键词：
GEF-H1; RhoA; Cytoskeleton rearrangements; Colon carcinoma; NUCLEOTIDE EXCHANGE FACTOR; COLORECTAL-CANCER; CELL INVASION; MICROTUBULES; HEPARANASE; PAXILLIN;
D O I：
10.1016/j.prp.2019.02.008
中图分类号：
R36 [病理学];
学科分类号：
100104 ;
摘要：
Colorectal cancer (CRC) is the third most common malignancy and a leading cause of cancer-related death worldwide. GEF-H1 is considered a RhoA-specific guanine nucleotide exchange factor. GEF-Hi upregulation may contribute to cancer cell migration and invasion and tumor progression. However, the expression and role of GEF-H1 in CRC have not yet been elucidated. This study attempted to elucidate how GEF-H1 drives tumor formation, motility, invasion and metastasis in colon cancer (CC). The expression of GEF-H1 in CC tissue microarrays (TMAs) was analyzed by immunohistochemistry (IHC). GEF-H1 was upregulated in CC tissues compared with adjacent non-tumoral tissues. In addition, we found that high GEF-H1 expression correlated with shorter overall survival and distant metastasis. Migration and invasion assays showed that GEF-H1 upregulation increased CC cell motility, invasion and metastasis. In contrast, functional knockdown of GEF-H1 by RNAi rescued the effects caused by GEF-H1 overexpression in CC cells. Overexpression of GEF-H1 re-organized the actin cytoskeleton, with increased punctate paxillin staining and F-actin stress fibers. Furthermore, western blotting showed that RhoA activation triggered by GEF-Hi overexpression caused phosphorylation of its downstream target, MLC2, in CC cells. In summary, the present study revealed that GEF-H1 is upregulated in CC tissues and plays a key role in CC metastasis through the GEF-H1-RhoA-MLC2 signaling pathway.
引用
收藏
页码：1012 / 1019
页数：8
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