Journal
CELL ADHESION & MIGRATION
Volume 11, Issue 3, Pages 205-210Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19336918.2016.1202385
Keywords
ALK; brain development; cell migration; PI3K; RNAi
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Funding
- NRF grant - Korean government (MSIP) [2015R1A2A1A10051958, 2008-0062282]
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Recently, unbiased functional genetic selection identified novel cell migration-regulating genes. This RNAi-based functional selection was performed using 63,996 pooled lentiviral shRNAs targeting 21,332 mouse genes. After five rounds of selection using cells with accelerated or impaired migration, shRNAs were retrieved and identified by half-hairpin barcode sequencing using cells with the selected phenotypes. This selection process led to the identification of 29 novel cell migration regulators. One of these candidates, anaplastic lymphoma kinase (ALK), was further investigated. Subsequent studies revealed that ALK promoted cell migration through the PI3K-AKT pathway via the p55 regulatory subunit of PI3K, rather than more commonly used p85 subunit. Western blot and immunohistochemistry studies using mouse brain tissues revealed similar temporal expression patterns of ALK, phospho-p55, and phospho-AKT during different stages of development. These data support an important role for the p55 subunit of PI3K in ALK-induced cell migration during brain development.
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