title: ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules.
abstract: Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated. In the present study, we aimed to investigate the influence of ST3Gal III on key steps in the process of breast cancer metastasis. ST3Gal III-overexpressing and ST3Gal III-silenced breast cancer MDA-MB-231 cell lines were generated. They showed an increase or decrease in the tumor-associated antigen sialyl-Lewis X (SLeX). The E-selectin binding capacity of the transfectants was proportional to cell surface SLeX levels. Cell migration and invasion were positively correlated with ST3Gal III levels. Moreover, ST3Gal III expression modulated the protein expression of invasion-related molecules, including β1 integrin, matrix metalloproteinase (MMP)-2, MMP-9 and cyclooxygenase-2, which may account for the mechanism involved in the effects of ST3Gal III on breast cancer invasiveness. In conclusion, our findings in these novel models of ST3Gal III expression revealed a critical requirement for ST3Gal III in several steps of breast cancer metastasis. ST3Gal III modulates breast cancer cell adhesion and invasion by altering the expression of invasion-related molecules. This study provides novel insights into the mechanisms underlying metastasis and suggests a new target for the effective drug treatment of breast cancer metastasis.
authors: Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161042, P.R. China.
authors: Hong-Xia
authors: HX
authors: Cui
authors: Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161042, P.R. China.
authors: Honglan
authors: H
authors: Wang
authors: Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161042, P.R. China.
authors: Yuchun
authors: Y
authors: Wang
authors: Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161042, P.R. China.
authors: Juan
authors: J
authors: Song
authors: Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161042, P.R. China.
authors: Hua
authors: H
authors: Tian
authors: Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161042, P.R. China.
authors: Chunhui
authors: C
authors: Xia
authors: The First Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China.
authors: Yetong
authors: Y
authors: Shen
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012799:Sialyltransferases / Q000502:physiology*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D019040:E-Selectin; D019012:Integrin beta1; D016256:Lewis X Antigen; C546936:SELE protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D012799:Sialyltransferases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human