Cell surface localization of importin α1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling

Sci Rep. 2016 Feb 18:6:21410. doi: 10.1038/srep21410.

Abstract

Importin α1 is involved in nuclear import as a receptor for proteins with a classical nuclear localization signal (cNLS). Here, we report that importin α1 is localized to the cell surface in several cancer cell lines and detected in their cultured medium. We also found that exogenously added importin α1 is associated with the cell membrane via interaction with heparan sulfate. Furthermore, we revealed that the cell surface importin α1 recognizes cNLS-containing substrates. More particularly, importin α1 bound directly to FGF1 and FGF2, secreted cNLS-containing growth factors, and addition of exogenous importin α1 enhanced the activation of ERK1/2, downstream targets of FGF1 signalling, in FGF1-stimulated cancer cells. Additionally, anti-importin α1 antibody treatment suppressed the importin α1-FGF1 complex formation and ERK1/2 activation, resulting in decreased cell growth. This study provides novel evidence that functional importin α1 is located at the cell surface, where it accelerates the proliferation of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation*
  • Fibroblast Growth Factor 1 / genetics
  • Fibroblast Growth Factor 1 / metabolism*
  • Hep G2 Cells
  • Humans
  • MAP Kinase Signaling System*
  • MCF-7 Cells
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*

Substances

  • KPNA2 protein, human
  • Neoplasm Proteins
  • alpha Karyopherins
  • Fibroblast Growth Factor 1
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3