Calreticulin activates β1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells

Yi Chien Lu, Chiung Nien Chen, Chia Ying Chu, Jen Her Lu, Bo Jeng Wang, Chia Hua Chen, Min Chuan Huang, Tsui Hwa Lin, Chin Chen Pan, Swey Shen Alex Chen, Wen Ming Hsu, Yung Feng Liao, Pei Yi Wu, Hsin Yi Hsia, Cheng Chi Chang, Hsinyu Lee

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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 ß1 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 inCRT-RNAi cells resulted in increased levels of ß1 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 ß1 integrin. These results indicated that α1,2-fucosylation of ß1 integrin was not involved in integrin-collagen interaction, but promoted ß1 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 ß1 integrin. Furthermore, increased fucosylation levels activate ß1 integrin, rather than directly modifying the integrin-binding sites.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalBiochemical Journal
Volume460
Issue number1
DOIs
Publication statusPublished - May 15 2014
Externally publishedYes

Keywords

  • Activation
  • Adhesion calreticulin
  • Fucosylation
  • Fucosyltransferase 1 (FUT1)
  • Integrin
  • RNA stability

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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