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GALNT14 mediates tumor invasion and migration in breast cancer cell MCF‐7
Author(s) -
Huanna Tian,
Tao Zuo,
Xiangfei Wang,
Longfei An,
Yuanyuan Xie,
Jianhua Wang,
Cuifang Zhang,
Manjing Jiao,
Wenjing Cao,
Shaochuan Qin,
Feifei Xu,
Naikang Li,
Jinchao Zhang,
Chen Wu
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22186
Subject(s) - biology , gene knockdown , vimentin , downregulation and upregulation , cancer research , cell migration , mcf 7 , cell growth , cancer cell , cell , cell culture , cancer , immunology , gene , immunohistochemistry , biochemistry , genetics , human breast
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. © 2014 Wiley Periodicals, Inc.