RNAi-based functional selection identifies novel cell migration determinants dependent on PI3K and AKT pathways

Minchul Seo, Shinrye Lee, Jong-Heon Kim, Won-Ha Lee, Guang Hu, Stephen J. Elledge and Kyoungho Suk ()
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Minchul Seo: Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine
Shinrye Lee: Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine
Jong-Heon Kim: Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine
Won-Ha Lee: KNU Creative BioResearch Group, School of Life Sciences and Biotechnology, Kyungpook National University
Guang Hu: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health and Sciences
Stephen J. Elledge: Howard Hughes Medical Institute, Brigham and Women’s Hospital, Harvard Medical School
Kyoungho Suk: Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract Lentiviral short hairpin RNA (shRNA)-mediated genetic screening is a powerful tool for identifying loss-of-function phenotype in mammalian cells. Here, we report the identification of 91 cell migration-regulating genes using unbiased genome-wide functional genetic selection. Individual knockdown or cDNA overexpression of a set of 10 candidates reveals that most of these cell migration determinants are strongly dependent on the PI3K/PTEN/AKT pathway and on their downstream signals, such as FOXO1 and p70S6K1. ALK, one of the cell migration promoting genes, uniquely uses p55γ regulatory subunit of PI3K, rather than more common p85 subunit, to trigger the activation of the PI3K-AKT pathway. Our method enables the rapid and cost-effective genome-wide selection of cell migration regulators. Our results emphasize the importance of the PI3K/PTEN/AKT pathway as a point of convergence for multiple regulators of cell migration.

Date: 2014
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DOI: 10.1038/ncomms6217

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