title: GALNT14 mediates tumor invasion and migration in breast cancer cell MCF-7.
abstract: Aberrant glycosylation is a hallmark of most human cancers and affects many cellular properties, including cell proliferation, apoptosis, differentiation, transformation, migration, invasion, and immune responses. Here, we report that N-acetylgalactosaminyltransferase14 (GALNT14), which mediates the initial step of mucin-type O-glycosylation and is heterogeneously expressed in most breast cancers, plays a critical role in the invasion and migration of breast cancers by regulating the activity of MMP-2 and expression of some EMT genes. We have modulated the expression of GALNT14 by RNAi and overexpression in MCF-7 cells. Overexpression of GALNT14 significantly enhanced cell migration and invasion and promoted the proliferation of breast cancer cells. Knockdown of GALNT14 reduced clonogenicity and attenuates cell migration and cell invasion. The mRNAs for N-cadherin, vimentin, E-cadherin, MMP-2, VEGF, and TGF-β were determined by RT-qPCR involving GALNT14-overexpressing or knockdown MCF-7 cells. Expression profiling revealed the upregulation of N-cadherin, vimentin, MMP-2, VEGF, TGF-β and the downregulation of E-cadherin in GALNT14 overexpressing cells, with the opposite seen in GALNT14 knockdowns. Gelatin zymography analysis further indicated that overexpression of GALNT14 increased MMP-2 activity in MCF-7 cells. Conversely, downregulation of GALNT14 reduced MMP-2 activity. Promoter analysis revealed that GALNT14 stimulates MMP-2 expression through the AP-1-binding site. Western blot analyses showed that knockdown of GALNT14 significantly reduced the expression of an oncoprotein mucin 1 (MUC1). These findings indicate that GALNT14 contributes to breast cancer invasion by altering the cell proliferation, motility, expression levels of EMT genes, and by stimulating MMP-2 activity, suggesting GALNT14 may be a potential target for breast cancer treatment.
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.|Basic Medical Institute, Chengde Medical College, Chengde, Hebei, PR China.
authors: Tian
authors: T
authors: Huanna
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Zuo
authors: Z
authors: Tao
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Wang
authors: W
authors: Xiangfei
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: An
authors: A
authors: Longfei
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Xie
authors: X
authors: Yuanyuan
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Wang
authors: W
authors: Jianhua
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Zhang
authors: Z
authors: Cuifang
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Jiao
authors: J
authors: Manjing
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Cao
authors: C
authors: Wenjing
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Qin
authors: Q
authors: Shaochuan
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Xu
authors: X
authors: Feifei
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.
authors: Li
authors: L
authors: Naikang
authors: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, Hebei, PR China.|Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei, PR China.
authors: Zhang
authors: Z
authors: Jinchao
authors: College of Life Sciences, Hebei University, Baoding, Hebei, PR China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, Hebei, PR China.
authors: Wu
authors: W
authors: Chen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D018396:Mucin-1 / Q000235:genetics; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014746:Vimentin / Q000235:genetics; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D015820:Cadherins; D020778:Matrix Metalloproteinase 2; D018396:Mucin-1; D017350:N-Acetylgalactosaminyltransferases; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D000097763:Polypeptide N-acetylgalactosaminyltransferase
keywords: EMT genes; GALNT14; MCF-7 cells; MMP-2; MUC1; invasion; migration