Fer kinase regulates cell migration through α-dystroglycan glycosylation

Tohru Yoneyama, Kiyohiko Angata, Xingfeng Bao, Sara Courtneidge, Sumit K. Chanda, Minoru Fukuda

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Glycans of α-dystroglycan (α-DG), which is expressed at the epithelial cell-basement membrane (BM) interface, play an essential role in epithelium development and tissue organization. Laminin-binding glycans on α-DG expressed on cancer cells suppress tumor progression by attenuating tumor cell migration from the BM. However, mechanisms controlling laminin-binding glycan expression are not known. Here, we used small interfering RNA (siRNA) library screening and identified Fer kinase, a non-receptor-type tyrosine kinase, as a key regulator of laminin-binding glycan expression. Fer overexpression decreased laminin- binding glycan expression, whereas siRNA-mediated down-regulation of Fer kinase increased glycan expression on breast and prostate cancer cell lines. Loss of Fer kinase function via siRNA or mutagenesis increased transcription levels of glycosyltransferases, including protein O-mannosyltransferase 1, β3-N-acetylglucosaminyltransferase 1, and like-acetylglucosaminyltransferase that are required to synthesize laminin-binding glycans. Consistently, inhibition of Fer expression decreased cell migration in the presence of laminin fragment. Fer kinase regulated STAT3 phosphorylation and consequent activation, whereas knockdown of STAT3 increased laminin-binding glycan expression on cancer cells. These results indicate that the Fer pathway negatively controls expression of genes required to synthesize lamininbinding glycans, thus impairing BM attachment and increasing tumor cell migration.

Original languageEnglish (US)
Pages (from-to)771-780
Number of pages10
JournalMolecular Biology of the Cell
Volume23
Issue number5
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

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Dystroglycans
Glycosylation
Cell Movement
Polysaccharides
Laminin
Phosphotransferases
Basement Membrane
Small Interfering RNA
Neoplasms
Glycosyltransferases
Mutagenesis
Protein-Tyrosine Kinases
Prostatic Neoplasms
Down-Regulation
Epithelium
Epithelial Cells
Phosphorylation
Cell Membrane
Breast Neoplasms
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Fer kinase regulates cell migration through α-dystroglycan glycosylation. / Yoneyama, Tohru; Angata, Kiyohiko; Bao, Xingfeng; Courtneidge, Sara; Chanda, Sumit K.; Fukuda, Minoru.

In: Molecular Biology of the Cell, Vol. 23, No. 5, 01.03.2012, p. 771-780.

Research output: Contribution to journalArticle

Yoneyama, Tohru ; Angata, Kiyohiko ; Bao, Xingfeng ; Courtneidge, Sara ; Chanda, Sumit K. ; Fukuda, Minoru. / Fer kinase regulates cell migration through α-dystroglycan glycosylation. In: Molecular Biology of the Cell. 2012 ; Vol. 23, No. 5. pp. 771-780.
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