title: Down-regulation of α-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface.
abstract: α-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels were detected by real-time PCR, and there was a greater than 139-fold increase in FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4, *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced using the immunohistochemical staining H-score method (*P < 0.001). Statistical analysis revealed that lower FUCA1 levels significantly predicted an inferior overall survival rate among triple-negative breast cancer (TNBC) patients compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down MDA-MB-231 cell lines were established, and the results suggest that transient FUCA inhibition creates a selective pressure that triggers the metastasis of primary tumor cells, as detected by wound healing and invasion assays (*P < 0.01). The results suggest that FUCA1 may be a potential prognostic molecular target for clinical use, especially in TNBC patients.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tzu-Chun
authors.initials: TC
authors.lastname: Cheng
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Chen
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wen-Ye
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Biological Statistics and Research Consultation Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Kuang
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shyr-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan.|Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D053938:DNA Fragmentation; D015536:Down-Regulation; D005260:Female; D005643:Fucose / Q000737:chemistry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D006868:Hydrolysis; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008875:Middle Aged; D009362:Neoplasm Metastasis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005644:alpha-L-Fucosidase / Q000378:metabolism*
chemical_list: C000593239:FUCA1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005643:Fucose; D005644:alpha-L-Fucosidase
keywords: glycosylation; metastasis; overall survival rate; triple-negative breast cancer; α-L-fucosidase