title: TRPM4 enhances cell proliferation through up-regulation of the β-catenin signaling pathway.
abstract: Altered expression of some members of the TRP ion channel superfamily has been associated with the development of pathologies like cancer. In particular, TRPM4 levels are reportedly elevated in diffuse large B-cell non-Hodgkin lymphoma, prostate, and cervical cancer. However, whether such changes in TRPM4 expression may be relevant to genesis or progression of cancer remains unknown. Here we show that reducing TRPM4 expression decreases proliferation of HeLa cells, a cervical cancer-derived cell line. In this cell line, constitutive TRPM4 silencing promoted GSK-3β-dependent degradation of β-catenin and reduced β-catenin/Tcf/Lef-dependent transcription. Conversely, overexpression of TRPM4 in T-REx 293 cells (a HEK293-derived cell line) increased cell proliferation and β-catenin levels. Our results identify TRPM4 as an important, unanticipated regulator of the β-catenin pathway, where aberrant signaling is frequently associated with cancer.
authors.affiliation: Centro de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, Santiago, Chile. rarmisen@bitmed.med.uchile.cl
authors.forename: Ricardo
authors.initials: R
authors.lastname: Armisén
authors.forename: Katherine
authors.initials: K
authors.lastname: Marcelain
authors.forename: Felipe
authors.initials: F
authors.lastname: Simon
authors.forename: Julio C
authors.initials: JC
authors.lastname: Tapia
authors.forename: Jessica
authors.initials: J
authors.lastname: Toro
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
authors.forename: Andrés
authors.initials: A
authors.lastname: Stutzin
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D051176:beta Catenin