Abstract
The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions of TPC2 and a discussion of its potential as a target for therapeutic intervention, including a summary of clinical trials examining the TPC2 inhibitors, naringenin, tetrandrine, and verapamil for the treatment of various cancers is provided.
Highlights
Ca2+ is a major second messenger in cells and alterations in intracellular Ca2+ signaling regulate a variety of biological processes, including exocytosis/endocytosis, cell proliferation, invasion, migration, and apoptosis
Many different types of Ca2+-channels are found in cells; some are expressed on the plasma membrane [e.g., voltage-gated Ca2+ channels, transient receptor potential (TRP) channels, and store-operated channels], whereas others are expressed on the membrane of intracellular organelles, such as ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3R) located on the sarcoplasmic and endoplasmic
TPC2 can associate with the leucinerich repeat kinase 2 (LRRK2), mutations in which are linked to late-onset Parkinson’s disease [20], and the mammalian target of rapamycin, a serine/threonine protein kinase that when hyperactivated leads to increased growth and proliferation [10]
Summary
Cite this article: Skelding KA, Barry DL, Theron DZ, Lincz LF. Targeting the two-pore channel 2 in cancer progression and metastasis.
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