Cell Surface Localization Of Importin Alpha 1/Kpna2 Affects Cancer Cell Proliferation By Regulating Fgf1 Signalling

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