Clinical and Translational Sciences Institute, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
The Queen's Medical Center and University of Hawaii, Honolulu, HI 96813, USA.
Cells. 2020 Feb 7;9(2):388. doi: 10.3390/cells9020388.
Calcium ions (Ca) play an important role as second messengers in regulating a plethora of physiological and pathological processes, including the progression of cancer. Several selective and non-selective Ca-permeable ion channels are implicated in mediating Ca signaling in cancer cells. In this review, we are focusing on TRPC1, a member of the TRP protein superfamily and a potential modulator of store-operated Ca entry (SOCE) pathways. While TRPC1 is ubiquitously expressed in most tissues, its dysregulated activity may contribute to the hallmarks of various types of cancers, including breast cancer, pancreatic cancer, glioblastoma multiforme, lung cancer, hepatic cancer, multiple myeloma, and thyroid cancer. A range of pharmacological and genetic tools have been developed to address the functional role of TRPC1 in cancer. Interestingly, the unique role of TRPC1 has elevated this channel as a promising target for modulation both in terms of pharmacological inhibition leading to suppression of tumor growth and metastasis, as well as for agonistic strategies eliciting Caoverload and cell death in aggressive metastatic tumor cells.
钙离子(Ca)作为第二信使在调节多种生理和病理过程中发挥重要作用,包括癌症的进展。几种选择性和非选择性的 Ca 通透离子通道被认为参与调节癌细胞中的 Ca 信号转导。在这篇综述中,我们专注于 TRPC1,它是 TRP 蛋白超家族的一员,也是储存操作 Ca 内流(SOCE)途径的潜在调节剂。虽然 TRPC1 在大多数组织中广泛表达,但它的活性失调可能导致各种类型癌症的特征,包括乳腺癌、胰腺癌、多形性胶质母细胞瘤、肺癌、肝癌、多发性骨髓瘤和甲状腺癌。已经开发了一系列药理学和遗传学工具来解决 TRPC1 在癌症中的功能作用。有趣的是,TRPC1 的独特作用使该通道成为一种有前途的调节靶点,无论是在药理学抑制导致肿瘤生长和转移抑制方面,还是在激动剂策略引起侵袭性转移性肿瘤细胞 Ca 过载和细胞死亡方面。