Abstract:
The abnormal expression of Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) is closely related to the progression of multiple tumors. In addition, TRPV4 is increasingly being considered a potential target for cancer therapy, especially in tumor metastasis prevention. However, the biological correlation between TRPV4 and tumor metastasis, as well as the specific role of TRPV4 in malignant melanoma metastasis, is poorly understood. In this study, we aimed to examine the role of TRPV4 in melanoma metastasis through experiments and clinical data analysis, and the underlying anticancer mechanism of Baicalin, a natural compound, and its inhibitory effect on TRPV4 with in vivo and in vitro experiments. Our findings suggested that TRPV4 promotes metastasis in melanoma by regulating cell motility via rearranging the cytoskeletal, and Baicalin can inhibit cancer metastasis, whose mechanisms reverse the recruitment of activated cofilin to leading-edge protrusion and the increasing phosphorylation level of cortactin, which is provoked by TRPV4 activation.
摘要:
瞬时受体电位阳离子通道亚家族V成员4(TRPV4)的异常表达与多种肿瘤的进展密切相关。此外,TRPV4越来越被认为是癌症治疗的潜在靶点。尤其是在肿瘤转移预防方面。然而,TRPV4与肿瘤转移的生物学相关性,以及TRPV4在恶性黑色素瘤转移中的具体作用,知之甚少。在这项研究中,我们旨在通过实验和临床数据分析来研究TRPV4在黑色素瘤转移中的作用,以及黄芩苷的潜在抗癌机制,一种天然化合物,体内外实验及其对TRPV4的抑制作用。我们的发现表明,TRPV4通过重排细胞骨架调节细胞运动来促进黑色素瘤的转移,黄芩苷可以抑制癌症转移,其机制逆转激活的cofilin募集到前缘突起和cortactin磷酸化水平的增加,这是由TRPV4激活引起的。