title: ORAI3 silencing alters cell proliferation and cell cycle progression via c-myc pathway in breast cancer cells.
abstract: Members of the Orai family are highly selective calcium ion channels that play an important role in store-operated calcium entry. Among the three known Orai isoforms, Orai3 has gained increased attention, notably for its emerging role in cancer. We recently demonstrated that Orai3 channels are over-expressed in breast cancer (BC) biopsies, and involved specifically in proliferation, cell cycle progression and survival of MCF-7 BC cells. Here, we investigate the downstream signaling mechanisms affected by Orai3 silencing, leading to the subsequent functional impact specifically seen in MCF-7 cancer cells. We report a correlation between Orai3 and c-myc expression in tumor tissues and in the MCF-7 cancer cell line by demonstrating that Orai3 down-regulation reduces both expression and activity of the proto-oncogene c-myc. This is likely mediated through the MAP Kinase pathway, as we observed decreased pERK1/2 levels and cell-cycle arrest in G1 phase after Orai3 silencing. Our results provide strong evidence that the c-myc proto-oncogene is influenced by the store-operated calcium entry channel Orai3 through the MAP kinase pathway. This connection provides new clues in the downstream mechanism linking Orai3 channels and proliferation, cell cycle progression and survival of MCF-7 BC cells.
authors.affiliation: University of Picardie Jules Verne, UFR of Sciences, Laboratory of Cellular and Molecular Physiology EA 4667, SFR CAP-SANTE, Amiens, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Faouzi
authors.forename: Philippe
authors.initials: P
authors.lastname: Kischel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Hague
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ahidouch
authors.forename: Nazim
authors.initials: N
authors.lastname: Benzerdjeb
authors.forename: Henri
authors.initials: H
authors.lastname: Sevestre
authors.forename: Reinhold
authors.initials: R
authors.lastname: Penner
authors.forename: Halima
authors.initials: H
authors.lastname: Ouadid-Ahidouch
mesh_terms: D000230:Adenocarcinoma; D017209:Apoptosis; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D016193:G1 Phase / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D015220:Calcium Channels; C000715470:MAS1 protein, human; C522867:Orai3 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium