Extracellular galectin-3 programs multidrug resistance through Na+/K+-ATPase and P-glycoprotein signaling.

摘要: // Yosuke Harazono 1, 2 , Dhong Hyo Kho 1 Vitaly Balan 3 Kosei Nakajima Victor Hogan Avraham Raz Departments of Oncology and Pathology, School Medicine, Wayne State University, Karmanos Cancer Institute, Detroit, MI 48201, USA Department Maxillofacial Surgery, Tokyo Medical Dental Bunkyo-ku, 113-8510, Japan Everon Biosciences, Buffalo, NY 14203, Correspondence to: Raz, e-mail: raza@karmanos.org Keywords: galectin-3, Na+/K+-ATPase, multidrug resistance, P-glycoprotein, phosphorylation Received: May 13, 2015      Accepted: June 05, Published: 17, 2015 ABSTRACT Galectin-3 (Gal-3, LGALS3) is a pleotropic versatile, 29–35 kDa chimeric gene product, involved in diverse physiological pathological processes, including cell growth, homeostasis, apoptosis, pre-mRNA splicing, cell-cell cell-matrix adhesion, cellular polarity, motility, activation, differentiation, transformation, signaling, regulation innate/adaptive immunity, angiogenesis. In multiple diseases, it was found that the level circulating Gal-3 markedly elevated, suggesting Gal-3-dependent function mediated by specific interaction with yet an unknown ubiquitous cell-surface protein. Recently, we showed attenuated drug-induced which one mechanisms underlying resistance (MDR). Here, document MDR could be house-keeping product e.g., Na + /K -ATPase, P-glycoprotein (P-gp). interacts -ATPase induces P-gp. We also find binds P-gp enhances its ATPase activity. Furthermore antagonist suppresses this results decrease activity P-gp, leading to increased sensitivity doxorubicin-mediated death. Taken together, these findings may explain reported roles diseases suggest combined therapy inhibitors Gal-3, disease drug(s) might superior single therapeutic modality.