鉴定 TRPV4 为结直肠癌侵袭的一个新靶点。
Identification of TRPV4 as a novel target in invasiveness of colorectal cancer.
机构信息
Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T., Institute of E.N.T, No. 3004 Longgang Avenue, Shenzhen, Guangdong, China.
School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
出版信息
BMC Cancer. 2021 Nov 23;21(1):1264. doi: 10.1186/s12885-021-08970-7.
BACKGROUND
Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown.
METHODS
Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1.
RESULTS
Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1.
CONCLUSIONS
Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.
背景
新出现的证据表明 TRPV4 在多种人类癌症中具有关键作用。然而，TRPV4 在结肠癌侵袭性中的潜在分子机制尚不清楚。
方法
免疫组织化学染色用于分析临床组织中 TRPV4 和 ZEB1 的表达；伤口愈合和 Transwell 分析用于确定细胞侵袭性；Western blot 用于探讨 TRPV4 和 ZEB1 之间的关系。
结果
用针对 TRPV4 的 siRNA 或 HC067047（一种选择性 TRPV4 拮抗剂）、TRPV4 全长质粒或针对 ZEB1 的 siRNA 转染结肠癌细胞，以测量细胞迁移和侵袭。我们发现 TRPV4 沉默或抑制对结肠癌细胞迁移和侵袭具有抑制作用，同时伴随着 EMT 过程的削弱和 AKT 活性的抑制。TRPV4 刺激 ZEB1 的表达，从而促进 EMT 过程和侵袭性。还发现临床局部转移患者中 TRPV4 和 ZEB1 的过表达，以及 TRPV4 和 ZEB1 之间存在正相关。
结论
我们的结果揭示了 TRPV4 在肿瘤转移中的作用，并强调了 TRPV4-ZEB1 轴在指示 EMT 中的潜在机制。
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