Uncovering the Signaling Landscape Controlling Breast Cancer Cell Migration Identifies Novel Metastasis Driver Genes

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jul 7

PMID 31278301

Citations 42

Authors

Esmee Koedoot

Michiel Fokkelman

Vasiliki-Maria Rogkoti

Marcel Smid

Iris van de Sandt

Hans de Bont

Chantal Pont

Janna E Klip

Steven Wink

Mieke A Timmermans

Erik A C Wiemer

Peter Stoilov

John A Foekens

Sylvia E Le Devedec

John W M Martens

Bob van de Water

Affiliations

Soon will be listed here.

Abstract

Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development.

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