KRT15 promotes colorectal cancer cell migration and invasion through β-catenin/MMP-7 signaling pathway

结直肠癌 癌症研究 细胞迁移 大肠癌小鼠模型的建立 癌基因 癌症 基因沉默 异位表达 癌细胞 转移 医学 生物 细胞 细胞培养 内科学 细胞周期 生物化学 遗传学 基因
作者
Weida Chen,Chengli Miao
出处
期刊:Medical Oncology [Springer Science+Business Media]
卷期号:39 (6) 被引量:18
标识
DOI:10.1007/s12032-021-01619-2
摘要

KRT15 has been reported to act as an oncogene in colorectal cancer. However, whether KRT15 promotes colorectal cancer migration and invasion remain unclear. In this study, western blot and qRT-PCR assay were used to determine the expression of KRT15 in colorectal cancer cells. Wound-healing and transwell migration assay were performed to assess the migration of colorectal cancer cells. Matrigel transwell invasion assay was employed to examine the invasion of colorectal cancer cells. We found that KRT15 was highly expressed in colorectal cancer cells. Ectopic expression of KRT15 dramatically promoted colorectal cancer cell migration and invasion. Conversely, silencing KRT15 remarkably suppressed the migration and invasion of colorectal cancer cells. Importantly, we found that MMP-7 was crucial for KRT15-induced migration and invasion of colorectal cancer cells. Knockdown of MMP-7 significantly diminished the migration and invasion induced by KRT15; overexpression of MMP-7 almost completely rescued the inhibitory effects of KRT15 shRNAs on colorectal cancer cell migration and invasion. In addition, by gain- and loss-of function, we confirmed that β-catenin was responsible for the increased expression of MMP-7 induced by KRT15 colorectal cancer cell lines. In conclusion, KRT15 promotes migration and invasion of colorectal cancer cell at least partly through β-catenin/MMP7 signaling pathway, suggesting KRT15 is a potential therapeutic target for patients with metastatic colorectal cancer.

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