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Cancer-associated exportin-6 upregulation inhibits the transcriptional repressive and anticancer effects of nuclear profilin-1

ABSTRACT: Aberrant expression of nuclear transporters and altered subcellular localization of their cargo proteins are increasingly recognized as drivers and therapeutic targets of cancer. Here, we report that exportin-6, a nuclear exporter specific for actin/profilin-1, is upregulated in a broad range of cancers and associated with poor prognosis. Exportin-6 loss triggers antitumor effects in breast cancer cells in a profilin-1-dependent fashion. Nuclear profilin-1 interacts with the Super Elongation Complex (SEC), a positive transcriptional regulator of pro-cancer genes including MYC. Exportin-6 loss, by increasing nuclear profilin-1, inhibits SEC-dependent transcription and sensitizes breast cancer cells to inhibition of BET domain proteins. Thus, exportin-6 upregulation is a previously unrecognized cancer addiction that reduces the transcriptional inhibitory and anticancer activities of nuclear profilin-1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144372 | GEO | 2021/04/07

REPOSITORIES: GEO

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Cancer-associated exportin-6 upregulation inhibits the transcriptional repressive and anticancer effects of nuclear profilin-1

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