Cell surface localization of importin ?1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling.

ABSTRACT: Importin ?1 is involved in nuclear import as a receptor for proteins with a classical nuclear localization signal (cNLS). Here, we report that importin ?1 is localized to the cell surface in several cancer cell lines and detected in their cultured medium. We also found that exogenously added importin ?1 is associated with the cell membrane via interaction with heparan sulfate. Furthermore, we revealed that the cell surface importin ?1 recognizes cNLS-containing substrates. More particularly, importin ?1 bound directly to FGF1 and FGF2, secreted cNLS-containing growth factors, and addition of exogenous importin ?1 enhanced the activation of ERK1/2, downstream targets of FGF1 signalling, in FGF1-stimulated cancer cells. Additionally, anti-importin ?1 antibody treatment suppressed the importin ?1-FGF1 complex formation and ERK1/2 activation, resulting in decreased cell growth. This study provides novel evidence that functional importin ?1 is located at the cell surface, where it accelerates the proliferation of cancer cells.

SUBMITTER: Yamada K 

PROVIDER: S-EPMC4757827 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other