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
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Tzu-Chun Cheng1, Shih-Hsin Tu2,*, Li-Ching Chen3,4, Ming-Yao Chen3, Wen-Ye Chen5, Yen-Kuang Lin6, Chi-Tang Ho7, Shyr-Yi Lin8,*, Chih-Hsiung Wu2,9 and Yuan-Soon Ho1,5,10,11
1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
2 Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3 Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
4 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
5 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
6 Biological Statistics and Research Consultation Center, Taipei Medical University, Taipei, Taiwan
7 Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA
8 Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
9 Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
10 Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan
11 Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan
* These authors have contributed equally to this manuscript
Yuan-Soon Ho, email:
Chih-Hsiung Wu, email:
Keywords: α-L-fucosidase, triple-negative breast cancer, overall survival rate, glycosylation, metastasis
Received: March 13, 2015 Accepted: May 02, 2015 Published: May 22, 2015
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.
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