A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration.

Abstract:

:To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways whose knockdown dramatically enhances cellular migration. Some of these pathways share features of epithelial-to-mesenchymal transition (EMT), and together they implicate key regulators of transcription, cellular signaling, and metabolism, as well as novel modulators of cellular trafficking, such as DLG5. In delineating downstream pathways mediating these migration phenotypes, we observed universal activation of ERKs and a profound dependence on their RSK effectors. Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration induced by knockdown of all 31 genes, suggesting that convergence of diverse migratory pathways on this kinase may provide a therapeutic opportunity in disorders of cell migration, including cancer metastasis.

journal_name

Genes Dev

journal_title

Genes & development

authors

Smolen GA,Zhang J,Zubrowski MJ,Edelman EJ,Luo B,Yu M,Ng LW,Scherber CM,Schott BJ,Ramaswamy S,Irimia D,Root DE,Haber DA

doi

10.1101/gad.1989110

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

2654-65

issue

23

eissn

0890-9369

issn

1549-5477

pii

gad.1989110

journal_volume

24

pub_type

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