DOI: 10.1101/479568Nov 30, 2018Paper

Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes

BioRxiv : the Preprint Server for Biology
Esmee KoedootBob van de Water

Abstract

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

Related Concepts

Malignant Neoplasm of Breast
Cell Motility
Diagnostic Imaging
Down-Regulation
Genes
Transcription Factor
Cell Line, Tumor
Carcinoma Breast Stage IV
Modulated
Subtype (Attribute)

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