title: RNAi screens for Rho GTPase regulators of cell shape and YAP/TAZ localisation in triple negative breast cancer.
abstract: In order to metastasise, triple negative breast cancer (TNBC) must make dynamic changes in cell shape. The shape of all eukaryotic cells is regulated by Rho Guanine Nucleotide Exchange Factors (RhoGEFs), which activate Rho-family GTPases in response to mechanical and informational cues. In contrast, Rho GTPase-activating proteins (RhoGAPs) inhibit Rho GTPases. However, which RhoGEFs and RhoGAPS couple TNBC cell shape to changes in their environment is very poorly understood. Moreover, whether the activity of particular RhoGEFs and RhoGAPs become dysregulated as cells evolve the ability to metastasise is not clear. Towards the ultimate goal of identifying RhoGEFs and RhoGAPs that are essential for TNBC metastasis, we performed an RNAi screen to isolate RhoGEFs and RhoGAPs that contribute to the morphogenesis of the highly metastatic TNBC cell line LM2, and its less-metastatic parental cell line MDA-MB-231. For ~6 million cells from each cell line, we measured 127 different features following the depletion of 142 genes. Using a linear classifier scheme we also describe the morphological heterogeneity of each gene-depleted population.
authors.affiliation: Dynamical Cell Systems Team, Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pascual-Vargas
authors.affiliation: Dynamical Cell Systems Team, Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.|Department of Computational Systems Medicine, Imperial College London, South Kensington Campus, London SW7, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Dynamical Cell Systems Team, Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Sero
authors.affiliation: Dynamical Cell Systems Team, Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Vicky
authors.initials: V
authors.lastname: Bousgouni
authors.affiliation: Dynamical Cell Systems Team, Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Mar
authors.initials: M
authors.lastname: Arias-Garcia
authors.affiliation: Dynamical Cell Systems Team, Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Chris
authors.identifier: 0000-0002-0413-6744
authors.initials: C
authors.lastname: Bakal
mesh_terms: D005260:Female; D020690:GTPase-Activating Proteins; D006801:Humans; D034622:RNA Interference; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000473:pathology
chemical_list: D020690:GTPase-Activating Proteins