School of Pharmacy, University of Camerino, via Madonna delle Carceri 9, 62032, Camerino, MC, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, via Madonna delle Carceri 9, 62032, Camerino, MC, Italy.
Lab Invest. 2020 Feb;100(2):186-198. doi: 10.1038/s41374-019-0333-7. Epub 2019 Oct 25.
Changes in transient receptor potential (TRP) Ca permeable channels are associated with development and progression of different types of cancer. Herein, we report data relative to the expression and function of TRP vanilloid 2 (TRPV2) channels in cancer. Overexpression of TRPV2 is observed in high-grade urothelial cancers and treatment with the TRPV2 agonist cannabidiol induces apoptosis. In prostate cancer, TRPV2 promotes migration and invasion, and TRPV2 overexpression characterizes the castration-resistant phenotype. In breast cancer cells, inhibition of TRPV2 by tranilast reduces the insulin-like growth factor-1 stimulated proliferation. TRPV2 overexpression in triple-negative breast cancer cells is associated with high recurrence-free survival. Increased TRPV2 overexpression is present in patients with esophageal squamous cell carcinoma associated with advanced disease, lymph node metastasis, and poor prognosis. Increased TRPV2 transcripts have been found both in benign hepatoma and in hepatocarcinomas, where TRPV2 expression is associated with portal vein invasion and reduction of cancer stem cell expression. TRPV2 expression and function has been also evaluated in gliomagenesis. This receptor negatively controls survival, proliferation, and resistance to CD95- or BCNU-induced apoptosis. In glioblastoma stem cells, TRPV2 activation promotes differentiation and inhibits the proliferation in vitro and in vivo. In glioblastoma, the TRPV2 is part of an interactome-based signature complex, which is negatively associated with survival, and it is expressed in high risk of recurrence and temozolomide-resistant patients. Finally, also in hematological malignancies, such as myeloma or acute myeloid leukemia, TRPV2 might represent a target for novel therapeutic approaches. Overall, these findings demonstrate that TRPV2 exhibits an oncogenic activity in different types of cancers, controlling survival, proliferation, migration, angiogenesis, and invasion signaling pathways. Thus, it prompts the pharmacological use of TRPV2 targeting in the control of cancer progression.
瞬时受体电位 (TRP) Ca 通透性通道的变化与不同类型癌症的发生和发展有关。本文报告了与癌症中 TRP 香草素 2 (TRPV2) 通道的表达和功能相关的数据。在高级尿路上皮癌中观察到 TRPV2 的过表达，并且 TRPV2 激动剂大麻二酚的治疗诱导细胞凋亡。在前列腺癌中，TRPV2 促进迁移和侵袭，并且 TRPV2 的过表达特征是去势抵抗表型。在乳腺癌细胞中，曲尼司特抑制 TRPV2 减少胰岛素样生长因子-1 刺激的增殖。三阴性乳腺癌细胞中 TRPV2 的过表达与无复发生存率高相关。与晚期疾病、淋巴结转移和预后不良相关的食管鳞状细胞癌患者中存在 TRPV2 过表达增加。良性肝癌和肝癌中均发现 TRPV2 转录本增加，其中 TRPV2 表达与门静脉侵犯和癌症干细胞表达减少相关。TRPV2 的表达和功能也在神经胶质瘤发生中进行了评估。该受体负调控存活、增殖和对 CD95 或 BCNU 诱导的细胞凋亡的抵抗。在神经胶质瘤干细胞中，TRPV2 激活促进分化并抑制体外和体内的增殖。在神经胶质瘤中，TRPV2 是基于相互作用组的特征性复合物的一部分，与存活呈负相关，并且在高复发风险和替莫唑胺耐药患者中表达。最后，在血液恶性肿瘤中，如骨髓瘤或急性髓系白血病，TRPV2 可能成为新的治疗方法的靶点。总之，这些发现表明 TRPV2 在不同类型的癌症中表现出致癌活性，控制存活、增殖、迁移、血管生成和侵袭信号通路。因此，它促使使用 TRPV2 靶向药物控制癌症进展。
