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Review
. 2020 Feb 7;9(2):388.
doi: 10.3390/cells9020388.

The Role of TRPC1 in Modulating Cancer Progression

Osama M Elzamzamy  1 , Reinhold Penner  2 , Lori A Hazlehurst  3
Affiliations
Review

The Role of TRPC1 in Modulating Cancer Progression

Osama M Elzamzamy et al. Cells. .

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.

Keywords: EMT; SOCE; TRPC1; cancer progression.

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Conflict of interest statement

L.H. is a co-founder of Modulation Therapeutics Inc. which has a license to MTI-101 for treatment of cancer. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The store-operated Ca2+ entry pathway (SOCE). (A) SOCE is regulated by agonist binding to G-protein coupled receptors (GPCRs) or receptor tyrosine-kinases (RTKs), activating phospholipase Cβ (PLCβ) via Gq/11 and PLCγ via RTK-mediated signaling, resulting in the production of IP3 and DAG from the cleavage of plasma-membrane PIP2. IP3 depletes Ca2+ stores from the ER through the IP3R which is sensed by STIM1. (B) STIM molecules multimerize forming puncta and translocate to the ER–PM junction, co-assembling with the CRAC channel subunits ORAI1, activating the Ca2+ selective Icrac currents. Further, STIM1 forms the STIM1-ORAI1-TRPC1 complex activating cation non-selective Isoc currents.
Figure 2
Figure 2
Ca2+ entry through SOCE activates NFAT activation: Ca2+ entry through the Icrac channel binds calmodulin, leading to the activation of the phosphatase protein calcineurin, activating the transcription factor NFAT. Active NFAT is translocated to the nucleus, regulating the expression of genes promoting proliferation, migration, and survival.
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References

    1. Berridge M.J., Lipp P., Bootman M.D. The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 2000;1:11–21. doi: 10.1038/35036035. - DOI - PubMed
    1. Berridge M.J., Bootman M.D., Roderick H.L. Calcium signalling: Dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 2003;4:517–529. doi: 10.1038/nrm1155. - DOI - PubMed
    1. Chen Y.F., Chen Y.T., Chiu W.T., Shen M.R. Remodeling of calcium signaling in tumor progression. J. Biomed. Sci. 2013;20:23. doi: 10.1186/1423-0127-20-23. - DOI - PMC - PubMed
    1. Prevarskaya N., Skryma R., Shuba Y. Ion channels and the hallmarks of cancer. Trends Mol. Med. 2010;16:107–121. doi: 10.1016/j.molmed.2010.01.005. - DOI - PubMed
    1. Rizzuto R., Pozzan T. When calcium goes wrong: Genetic alterations of a ubiquitous signaling route. Nature Genet. 2003;34:135–141. doi: 10.1038/ng0603-135. - DOI - PubMed

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