IPO11 promotes bladder cancer progression by facilitating drebrin nuclear accumulation and upregulating drebrin/EB3 via ELF1

Importin-11 (IPO11), a member of the karyopherin family, plays a key but poorly understood role in bladder cancer (BCa) progression. This study identified 64 IPO11-specific binding proteins, including drebrin, in EJ cells by coimmunoprecipitation (co-IP) and mass spectrometry. Their interaction and colocalization in the cytoplasm and nucleus were confirmed by co-IP, pulldown and immunofluorescence assays. Immunohistochemical analysis revealed that high drebrin expression in BCa tissues correlated with malignant phenotypes and elevated IPO11 levels ; nuclear drebrin was detected in 16% of specimens and correlated with nuclear IPO11. In vitro, downregulation of drebrin significantly inhibited the migration of EJ and 5637 cells. Loss- and gain-of-function experiments demonstrated that IPO11 knockdown reduced total drebrin/EB3 levels and nuclear drebrin content, while IPO11 overexpression increased the expression of both proteins in total, cytoplasmic, and nuclear fractions. Analysis of 21 predicted drebrin/EB3 transcription factors by qPCR identified five (ELF1, GBX2, SP1, SPI1, SPIB) with over 50% reduced expression in both cell lines following IPO11 downregulation. Transcription activation assays, EMSA, and ChIP experiments confirmed ELF1 as a drebrin/EB3 transcription factor positively regulated by IPO11. These findings demonstrate that IPO11 promotes BCa progression by facilitating drebrin nuclear accumulation and upregulating drebrin/EB3 through ELF1-mediated transcriptional activation.