title: Altered expression of stromal interaction molecule (STIM)-calcium release-activated calcium channel protein (ORAI) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in cancer: will they become a new battlefield for oncotherapy?
abstract: The stromal interaction molecule (STIM)-calcium release-activated calcium channel protein (ORAI) and inositol 1,4,5-trisphosphate receptors (IP3Rs) play pivotal roles in the modulation of Ca(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes. Increasing evidence has implicated the dysregulation of STIM-ORAI and IP3Rs in tumorigenesis and tumor progression. By controlling the activities, structure, and/or expression levels of these Ca(2+)-transporting proteins, malignant cancer cells can hijack them to drive essential biological functions for tumor development. However, the molecular mechanisms underlying the participation of STIM-ORAI and IP3Rs in the biological behavior of cancer remain elusive. In this review, we summarize recent advances regarding STIM-ORAI and IP3Rs and discuss how they promote cell proliferation, apoptosis evasion, and cell migration through temporal and spatial rearrangements in certain types of malignant cells. An understanding of the essential roles of STIM-ORAI and IP3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, P. R. China.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, P. R. China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Xiu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, P. R. China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shan
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, P. R. China. proxu_510080@163.com.
authors.forename: Kang-Qing
authors.initials: KQ
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D000071739:Calcium Release Activated Calcium Channels / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000071739:Calcium Release Activated Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors
keywords: Ca2+; Calcium release-activated calcium channel protein (ORAI); Inositol 1,4,5-trisphosphate receptors (IP3Rs); Stromal interaction molecule (STIM); Tumorigenesis