Author ORCID Identifier

https://orcid.org/0000-0002-6937-9384

https://orcid.org/0000-0003-1189-7231

https://orcid.org/0000-0002-0615-9616

https://orcid.org/0000-0002-3428-3366

Document Type

Article

Publication Date

2019

College/Unit

School of Medicine

Department/Program/Center

Biochemistry

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

Source Citation

Koedoot, E., Fokkelman, M., Rogkoti, V.-M., Smid, M., van de Sandt, I., de Bont, H., Pont, C., Klip, J. E., Wink, S., Timmermans, M. A., Wiemer, E. A. C., Stoilov, P., Foekens, J. A., Le Dévédec, S. E., Martens, J. W. M., & van de Water, B. (2019). Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-11020-3

Comments

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2019

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