STIM and Orai proteins as novel targets for cancer therapy. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

• Published in: American Journal of Physiology: Cell Physiology Vol. 309; no. 7; pp. C457 - C469
• Main Authors: Vashisht, Ayushi, Trebak, Mohamed, Motiani, Rajender K
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.10.2015
• Subjects: Calcium; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Signaling; Cancer; Cell Adhesion Molecules - genetics; Cell Transformation, Neoplastic - pathology; Cells; Humans; Membrane Proteins - genetics; Molecules; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Neoplasm Proteins - genetics; Neoplasms - genetics; Neoplasms - pathology; Neoplasms - therapy; ORAI1 Protein; ORAI2 Protein; Proteins; Stromal Interaction Molecule 1; Stromal Interaction Molecule 2; Themes; Tumors; Orai1; cancer; STIM1; STIM2; Orai3; angiogenesis
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00064.2015

Calcium (Ca(2+)) regulates a plethora of cellular functions including hallmarks of cancer development such as cell cycle progression and cellular migration. Receptor-regulated calcium rise in nonexcitable cells occurs through store-dependent as well as store-independent Ca(2+) entry pathways. Stromal interaction molecules (STIM) and Orai proteins have been identified as critical constituents of both these Ca(2+) influx pathways. STIMs and Orais have emerged as targets for cancer therapeutics as their altered expression and function have been shown to contribute to tumorigenesis. Recent data demonstrate that they play a vital role in development and metastasis of a variety of tumor types including breast, prostate, cervical, colorectal, brain, and skin tumors. In this review, we will retrospect the data supporting a key role for STIM1, STIM2, Orai1, and Orai3 proteins in tumorigenesis and discuss the potential of targeting these proteins for cancer therapy.