| Literature DB >> 31278301 |
Esmee Koedoot1, Michiel Fokkelman1, Vasiliki-Maria Rogkoti1, Marcel Smid2, Iris van de Sandt1, Hans de Bont1, Chantal Pont1, Janna E Klip1, Steven Wink1, Mieke A Timmermans2, Erik A C Wiemer2, Peter Stoilov3, John A Foekens2, Sylvia E Le Dévédec1, John W M Martens2, Bob van de Water4.
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.Entities:
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Year: 2019 PMID： 31278301 PMCID： PMC6611796 DOI： 10.1038/s41467-019-11020-3
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919