title: TRPC1 protein channel is major regulator of epidermal growth factor receptor signaling.
abstract: TRP channels have been associated with cell proliferation and aggressiveness in several cancers. In particular, TRPC1 regulates cell proliferation and motility, two processes underlying cancer progression. We and others have described the mechanisms of TRPC1-dependent cell migration. However, the involvement of TRPC1 in cell proliferation remains unexplained. In this study, we show that siRNA-mediated TRPC1 depletion in non small cell lung carcinoma cell lines induced G(0)/G(1) cell cycle arrest resulting in dramatic decrease in cell growth. The expression of cyclins D1 and D3 was reduced after TRPC1 knockdown, pointing out the role of TRPC1 in G(1)/S transition. This was associated with a decreased phosphorylation and activation of EGFR and with a subsequent disruption of PI3K/Akt and MAPK downstream pathways. Stimulation of EGFR by its natural ligand, EGF, induced Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry through TRPC1. Ca(2+) entry through TRPC1 conversely activated EGFR, suggesting that TRPC1 is a component of a Ca(2+)-dependent amplification of EGF-dependent cell proliferation.
authors.affiliation: Laboratory of Cell Physiology, Institute of Neuroscience, Université Catholique de Louvain, Brussels 1200, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tajeddine
authors.forename: Philippe
authors.initials: P
authors.lastname: Gailly
mesh_terms: D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; C534696:CCND3 protein, human; D056743:Cyclin D3; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D019938:Cyclin D1; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium