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: Tzu-Chun Cheng, Shih-Hsin Tu, Li-Ching Chen, Ming-Yao Chen, Wen-Ye Chen, Yen-Kuang Lin, Chi-Tang Ho, Shyr-Yi Lin, Chih-Hsiung Wu, Yuan-Soon Ho
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 25 Pg. 21283-300 (Aug 28 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26204487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FUCA1 protein, human
• RNA, Messenger
• RNA, Small Interfering
• Fucose
• alpha-L-Fucosidase

Topics

• Aged
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Cell Survival
• DNA Fragmentation
• Down-Regulation
• Female
• Fucose (chemistry)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Glycosylation
• Humans
• Hydrolysis
• Immunohistochemistry
• Kaplan-Meier Estimate
• MCF-7 Cells
• Middle Aged
• Neoplasm Metastasis
• RNA Interference
• RNA, Messenger (metabolism)
• RNA, Small Interfering (metabolism)
• Real-Time Polymerase Chain Reaction
• Triple Negative Breast Neoplasms (drug therapy, metabolism)
• alpha-L-Fucosidase (metabolism)