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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy

Author(s): Francesco Moccia, Estella Zuccolo, Valentina Poletto, Ilaria Turin, Germano Guerra, Paolo Pedrazzoli, Vittorio Rosti, Camillo Porta and Daniela Montagna

Volume 23 , Issue 30 , 2016

Page: [3450 - 3480] Pages: 31

DOI: 10.2174/0929867323666160607111220

Price: $65


An increase in intracellular Ca2+ concentration plays a key role in the establishment of many cancer hallmarks, including aberrant proliferation, migration, invasion, resistance to apoptosis and angiogenesis. The dysregulation of Ca2+ entry is one of the most subtle mechanisms by which cancer cells overwhelm their normal counterparts and gain the adaptive advantages that result in tumour growth, vascularisation and dissemination throughout the organism. Both constitutive and agonist-induced Ca2+ influx may be mediated by store-dependent as well as store-independent Ca2+ entry routes. A growing body of evidences have shown that different isoforms of Stromal Interaction Molecules (Stim1) and Orai proteins, i.e. Stim1, Stim2, Orai1 and Orai3, underlie both pathways in cancer cells. The alteration in either the expression or the activity of Stim and Orai proteins has been linked to the onset and maintenance of tumour phenotype in many solid malignancies, including prostate, breast, kidney, esophageal, skin, brain, colorectal, lung and liver cancers. Herein, we survey the existing data in support of Stim and Orai involvement in tumourigenesis and provide the rationale to target them in cancer patients. Besides, we summarize the most recent advances in the identification of novel pharmacological tools that could be successfully used in clinical therapy.

Keywords: Stim, Orai, store-operated Ca2+ entry, Ca2+ release-activated Ca2+ current, cancer, metastasis, angiogenesis, proliferation, apoptosis.

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