title: Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells.
abstract: Fucosylation regulates various pathological events in cells. We reported that different levels of CRT (calreticulin) affect the cell adhesion and metastasis of bladder cancer. However, the precise mechanism of tumour metastasis regulated by CRT remains unclear. Using a DNA array, we identified FUT1 (fucosyltransferase 1) as a gene regulated by CRT expression levels. CRT regulated cell adhesion through α1,2-linked fucosylation of β1 integrin and this modification was catalysed by FUT1. To clarify the roles for FUT1 in bladder cancer, we transfected the human FUT1 gene into CRT-RNAi stable cell lines. FUT1 overexpression in CRT-RNAi cells resulted in increased levels of β1 integrin fucosylation and rescued cell adhesion to type-I collagen. Treatment with UEA-1 (Ulex europaeus agglutinin-1), a lectin that recognizes FUT1-modified glycosylation structures, did not affect cell adhesion. In contrast, a FUT1-specific fucosidase diminished the activation of β1 integrin. These results indicated that α1,2-fucosylation of β1 integrin was not involved in integrin-collagen interaction, but promoted β1 integrin activation. Moreover, we demonstrated that CRT regulated FUT1 mRNA degradation at the 3'-UTR. In conclusion, the results of the present study suggest that CRT stabilized FUT1 mRNA, thereby leading to an increase in fucosylation of β1 integrin. Furthermore, increased fucosylation levels activate β1 integrin, rather than directly modifying the integrin-binding sites.
authors.affiliation: *Department of Life Science, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lu
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Chu
authors.affiliation: ∥Department of Pediatrics and Pediatric Cardiology, Taipei Veterans General Hospital 112, Taiwan, Republic of China.
authors.forename: Jenher
authors.initials: J
authors.lastname: Lu
authors.affiliation: ¶Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, Republic of China.
authors.forename: Bo-Jeng
authors.initials: BJ
authors.lastname: Wang
authors.affiliation: **Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 106, Taiwan, Republic of China.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: **Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 106, Taiwan, Republic of China.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
authors.affiliation: *Department of Life Science, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors.forename: Tsui-Hwa
authors.initials: TH
authors.lastname: Lin
authors.affiliation: ††Department of Pathology, Taipei Veterans General Hospital 112, Taiwan, Republic of China.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Pan
authors.affiliation: ‡‡Department of Molecular Biology, the Scripps Research Institute, San Diego, CA 92037, U.S.A.
authors.forename: Swey-Shen Alex
authors.initials: SS
authors.lastname: Chen
authors.affiliation: §Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan, Republic of China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.affiliation: ¶Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, Republic of China.
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Liao
authors.affiliation: *Department of Life Science, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Wu
authors.affiliation: *Department of Life Science, National Taiwan University, Taipei 106, Taiwan, Republic of China.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Hsia
authors.affiliation: §§Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei 100, Taiwan, Republic of China.
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Chang
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D037282:Calreticulin / Q000096:biosynthesis*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D005647:Fucosyltransferases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D020871:RNA Stability / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D037282:Calreticulin; D005647:Fucosyltransferases; D019012:Integrin beta1; D000097631:Galactoside 2-alpha-L-fucosyltransferase