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Identification of novel cell migration-promoting genes by a functional genetic screen

Minchul Seo^*,, Won-Ha Lee and Kyoungho Suk^*,1,2

^* Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Cell Matrix Research Institute (CMRI), and

Department of Genetic Engineering, School of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea

¹ Correspondence: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. E-mail: ksuk{at}knu.ac.kr

Here we describe the identification of novel cell migration-promoting genes based on an unbiased functional genetic screen in cultured cells. After the introduction of the retroviral mouse brain cDNA library into NIH3T3 mouse fibroblast cells, migration-promoted cells were selected by a 3-dimensional migration assay using cell culture inserts. After 5 rounds of enrichment, cDNAs were retrieved from the cells with a selected phenotype. Cell migration-promoting activity was confirmed by independent migration assays for the retrieved cDNAs, among which further investigation was focused on coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (chchd2). Whereas overexpression of chchd2 promoted cell migration, knockdown of endogenous chchd2 expression reduced cell migration. Chchd2-induced cell migration was associated with augmented formation of actin stress fibers and focal adhesion, which was mediated through Akt, RhoA/ROCK, and Jnk pathways. CHCHD2 protein directly interacted with hyaluronic acid-binding protein 1 (HABP1) that possessed migration-suppressing activity. Intracellular localization and further functional studies suggested that CHCHD2 and HABP1 may mutually regulate each other to balance cell migration. Thus, chchd2 is a novel cell migration determinant identified by an in vitro functional genetic selection strategy. The selection method can also be useful for the isolation of genes that give other phenotypes of interest.—Seo, M., Lee, W.-H., Suk, K. Identification of novel cell migration-promoting genes by a functional genetic screen.

Key Words: chchd2 • hyaluronic acid-binding protein 1 • NIH3T3 mouse fibroblast cells • retroviral cDNA library

This article has been cited by other articles:

				H. Jeon, Y. Go, M. Seo, W.-H. Lee, and K. Suk Functional Selection of Phagocytosis-Promoting Genes: Cell Sorting-Based Selection J Biomol Screen, September 1, 2010; 15(8): 949 - 955. [Abstract] [Full Text] [PDF]