Cancer-associated Exportin-6 Upregulation Inhibits the Transcriptionally Repressive and Anticancer Effects of Nuclear Profilin-1

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Feb 17

PMID 33596420

Citations 8

Authors

Cuige Zhu

Sun-Joong Kim

Arshag Mooradian

Faliang Wang

Ziqian Li

Sean Holohan

Patrick L Collins

Keren Wang

Zhanfang Guo

Jeremy Hoog

Cynthia X Ma

Eugene M Oltz

Jason M Held

Jieya Shao

Affiliations

Soon will be listed here.

Abstract

Aberrant expression of nuclear transporters and deregulated subcellular localization of their cargo proteins are emerging as drivers and therapeutic targets of cancer. Here, we present evidence that the nuclear exporter exportin-6 and its cargo profilin-1 constitute a functionally important and frequently deregulated axis in cancer. Exportin-6 upregulation occurs in numerous cancer types and is associated with poor patient survival. Reducing exportin-6 level in breast cancer cells triggers antitumor effects by accumulating nuclear profilin-1. Mechanistically, nuclear profilin-1 interacts with eleven-nineteen-leukemia protein (ENL) within the super elongation complex (SEC) and inhibits the ability of the SEC to drive transcription of numerous pro-cancer genes including MYC. XPO6 and MYC are positively correlated across diverse cancer types including breast cancer. Therapeutically, exportin-6 loss sensitizes breast cancer cells to the bromodomain and extra-terminal (BET) inhibitor JQ1. Thus, exportin-6 upregulation is a previously unrecognized cancer driver event by spatially inhibiting nuclear profilin-1 as a tumor suppressor.

Citing Articles

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