The Role of TRPC1 in Modulating Cancer Progression
Osama M. Elzamzamy, Reinhold Penner, Lori A Hazlehurst
Abstract
Calcium ions (Ca2+) 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 Ca2+-permeable ion channels are implicated in mediating Ca2+ 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 Ca2+ 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 Ca2+ overload and cell death in aggressive metastatic tumor cells.