Jiangsu Key Laboratory for Pharmacolgy and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Int J Mol Sci. 2022 Dec 2;23(23):15155. doi: 10.3390/ijms232315155.
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.
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，特别是在预防肿瘤转移方面。然而，TRPV4 与肿瘤转移之间的生物学相关性，以及 TRPV4 在恶性黑色素瘤转移中的具体作用，尚不清楚。在这项研究中，我们旨在通过实验和临床数据分析研究 TRPV4 在黑色素瘤转移中的作用，并通过体内和体外实验研究天然化合物黄芩素的抗癌机制及其对 TRPV4 的抑制作用。我们的研究结果表明，TRPV4 通过调节细胞运动来促进黑色素瘤的转移，通过重新排列细胞骨架，而黄芩素可以抑制癌症转移，其机制是通过抑制 TRPV4 的激活来逆转激活的 cofilin 向前沿突起的募集和 cortactin 磷酸化水平的增加。
