title: Galectin-3 accelerates the progression of oral tongue squamous cell carcinoma via a Wnt/β-catenin-dependent pathway.
abstract: The purpose of this study was to elucidate the clinicopathological significance and mechanism of action of galectin-3 in oral tongue squamous cell carcinoma (OTSCC). Here, the expression of galectin-3 was quantified in OTSCC (n = 68) and paired OTSCC and normal surrounding tissues (n = 10) using immunohistochemical staining. Tca8113 OTSCC cells were transfected with a plasmid expressing galectin-3 cDNA or siRNA against galectin-3. Cell proliferation, migration and invasion were measured using the MTT assay, Matrigel-coated Transwell migration assay and wound healing assay. The effect of galectin-3 on the Wnt/β-catenin signaling pathway and epithelial mesenchymal transition (EMT) were investigated using a plasmid expressing the Wnt antagonist dickkopf 1 (DKK1) and Western blotting. Galectin-3 was expressed at significantly higher levels in OTSCC than the normal adjacent tissues; galectin-3 expression correlated strongly with pathological stage, pathological grade and lymph node invasion in OTSCC. Overexpression of galectin-3 promoted Tca8113 cell proliferation, migration and invasion, upregulated Wnt protein expression, activated β-catenin and induced the EMT; knockdown of galectin-3 had the opposite effects. Co-transfection of Tca8113 cells overexpressing galectin-3 with the Wnt antagonist DKK1 reduced the ability of galectin-3 to increase cell proliferation, migration and invasion, reduced upregulation of Wnt, inhibited β-catenin activation and abrogated the EMT, demonstrating that the Wnt/β-catenin signaling pathway mediated the effects of galectin-3. Galectin-3 plays an important role in the progression of OTSCC via activation of the Wnt/β-catenin signaling pathway.
authors.affiliation: State Key Laboratory of Oncology in South China and Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Dong Road, Guangzhou 510060, People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Chen
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Zhuang
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D037502:Galectin 3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D020298:U937 Cells; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C501126:DKK1 protein, human; D037502:Galectin 3; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin