Title:Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy
Volume: 23
Issue: 30
Author(s): Francesco Moccia, Estella Zuccolo, Valentina Poletto, Ilaria Turin, Germano Guerra, Paolo Pedrazzoli, Vittorio Rosti and Camillo Porta, Daniela Montagna
Affiliation:
关键词:
Stim
摘要: 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.
