Galectin-3 induces cell migration via a calcium-sensitive MAPK/ERK1/2 pathway

// Xiaoge Gao 1,2,* , Vitaly Balan 1,3,* , Guihua Tai 2 , Avraham Raz 1 1 Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 2 School of Life Sciences, Northeast Normal University, Changchun, PR China 3 Present address: Everon Biosciences, Buffalo, NY * These authors contributed equally to the work Correspondence: Avraham Raz, email: // Keywords : galectin-3, calcium ions, protein kinase C, extracellular signal regulated protein kinase1/2, cell migration Received : January 15, 2014 Accepted :February 17, 2014 Published : February 19, 2014 Abstract The presence and level of circulating galectin-3 (Gal-3), a member of the galectin family, is associated with diverse diseases ranging from heart failure, immune disorders to cancer metastasis and serves as a biomarker of diagnosis and treatment response. However, the mechanisms by which exogenous Gal-3 affects pathobiology events remain elusive. In the current study, we found that exogenous Gal-3 slightly delays, while prolonging tyrosine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cells through a calcium-sensitive and PKC-dependent signaling pathway. The activation was dependent on the sugar-binding properties of Gal-3, since the antagonist lactose could inhibit it. The sugar-binding motif of Gal-3 was required for the activation of ERK1/2. The activation of ERK1/2 was necessary for the initiation and induction of cell migration associated with the phosphorylation of paxillin. All the results presented in this study suggest a novel calcium-sensitive and PKC-dependent pathway through which circulating Gal-3 promotes cell migration and activating the ERK1/2. Taken together, the data depicted here propose a biological function and a target for the diseases’ associated circulating Gal-3.