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IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway
Author(s) -
Zhu Qiangqiang,
Wu Yiqi,
Yang Mengli,
Wang Zhen,
Zhang Hailing,
Jiang Xinying,
Chen Meng,
Jin Tianyu,
Wang Ting
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23098
Subject(s) - rhoa , biology , azoxymethane , metastasis , colorectal cancer , cancer research , medicine , cancer , endocrinology , microbiology and biotechnology , signal transduction , genetics
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. As tumor metastasis is the leading cause of death in patients with CRC, it is important to elucidate the molecular mechanisms that drive CRC metastasis. Studies have shown a close relationship between Iroquois homeobox (IRX) family genes and multiple cancers, while the mechanism by which IRX5 promotes CRC metastasis is unclear. Therefore, we focused on the involvement of IRX5 in CRC metastasis. In this study, analyses of clinical data indicated that the expression of IRX5 was coincided with metastatic colorectal tumors tissues and was negatively correlated with the overall survival of patients with CRC. Functional analysis showed that IRX5 promoted the migration and invasion of CRC cells, accompanied by a large number of cellular protrusions. IRX5‐overexpressing cells were more likely to form metastatic tumors in nude mice. Further analysis demonstrated that the core components of the RHOA/ROCK1/LIMK1 pathway were significantly inhibited in IRX5‐overexpressing cells. Overexpression of LIMK1 effectively reversed the enhanced cellular motility caused by IRX5 overexpression. Moreover, we found that high levels of IRX5 in intestinal tissues were correlated with the inflammatory response. IRX5 was significantly increased in azoxymethane/dextran sodium sulfate intestinal tissue of mice and IRX5‐overexpressing may also enhance chemokines CXCL1 and CXCL8. In summary, our findings suggested that IRX5 promoted CRC metastasis by inhibiting the RHOA‐ROCK1‐LIMK1 axis, which correlates with a poor prognosis.