MicroRNA 17/20 Inhibits Cellular Invasion and Tumor Metastasis in Breast Cancer by Heterotypic Signaling

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Apr 22

PMID 20406904

Citations 131

Authors

Zuoren Yu

Nicole E Willmarth

Jie Zhou

Sanjay Katiyar

Min Wang

Yang Liu

Peter A McCue

Andrew A Quong

Michael P Lisanti

Richard G Pestell

Affiliations

Soon will be listed here.

Abstract

microRNAs are thought to regulate tumor progression and invasion via direct interaction with target genes within cells. Here the microRNA17/20 cluster is shown to govern cellular migration and invasion of nearby cells via heterotypic secreted signals. microRNA17/20 abundance is reduced in highly invasive breast cancer cell lines and node-positive breast cancer specimens. Cell-conditioned medium from microRNA17/20-overexpressing noninvasive breast cancer cell MCF7 was sufficient to inhibit MDA-MB-231 cell migration and invasion through inhibiting secretion of a subset of cytokines, and suppressing plasminogen activation via inhibition of the secreted plasminogen activators (cytokeratin 8 and alpha-enolase). microRNA17/20 directly repressed IL-8 by targeting its 3' UTR, and inhibited cytokeratin 8 via the cell cycle control protein cyclin D1. At variance with prior studies, these results demonstrated a unique mechanism of how the altered microRNA17/20 expression regulates cellular secretion and tumor microenvironment to control migration and invasion of neighboring cells in breast cancer. These findings not only reveal an antiinvasive function of miR-17/20 in breast cancer, but also identify a heterotypic secreted signal that mediates the microRNA regulation of tumor metastasis.

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