TY - JOUR
T1 - TRPM4 enhances cell proliferation through up-regulation of the β-catenin signaling pathway
AU - Armisén, Ricardo
AU - Marcelain, Katherine
AU - Simon, Felipe
AU - Tapia, Julio C.
AU - Toro, Jessica
AU - Quest, Andrew F.G.
AU - Stutzin, Andrés
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78049294716&partnerID=8YFLogxK
U2 - 10.1002/jcp.22310
DO - 10.1002/jcp.22310
M3 - Article
C2 - 20625999
AN - SCOPUS:78049294716
SN - 0021-9541
VL - 226
SP - 103
EP - 109
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -