Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1.

TitleRegulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1.
Publication TypeJournal Article
Year of Publication2008
AuthorsMelani M, Simpson KJ, Brugge JS, Montell D
JournalCurr Biol
Volume18
Issue7
Pagination532-7
Date Published2008 Apr 08
ISSN0960-9822
KeywordsAnimals, Breast, Cell Adhesion, Cell Line, Cell Movement, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Epithelial Cells, Female, Humans, JNK Mitogen-Activated Protein Kinases, Morphogenesis, Nuclear Proteins, Ovary, Signal Transduction, STAT Transcription Factors, Transcription Factors
Abstract

<p>Cell movements represent a major driving force in embryonic development, tissue repair, and tumor metastasis [1]. The migration of single cells has been well studied, predominantly in cell culture [2, 3]; however, in vivo, a greater variety of modes of cell movement occur, including the movements of cells in clusters, strands, sheets, and tubes, also known as collective cell migrations [4, 5]. In spite of the relevance of these types of movements in both normal and pathological conditions, the molecular mechanisms that control them remain predominantly unknown. Epithelial follicle cells of the Drosophila ovary undergo several dynamic morphological changes, providing a genetically tractable model [6]. We found that anterior follicle cells, including border cells, mutant for the gene hindsight (hnt) accumulated excess cell-cell adhesion molecules and failed to undergo their normal collective movements. In addition, HNT affected border cell cluster cohesion and motility via effects on the JNK and STAT pathways, respectively. Interestingly, reduction of expression of the mammalian homolog of HNT, RREB1, by siRNA inhibited collective cell migration in a scratch-wound healing assay of MCF10A mammary epithelial cells, suppressed surface activity, retarded cell spreading after plating, and led to the formation of immobile, tightly adherent cell colonies. We propose that HNT and RREB1 are essential to reduce cell-cell adhesion when epithelial cells within an interconnected group undergo dynamic changes in cell shape.</p>

DOI10.1016/j.cub.2008.03.024
Alternate JournalCurr Biol
PubMed ID18394891
Grant ListR01 AG063907 / AG / NIA NIH HHS / United States
U54 GM064346 / GM / NIGMS NIH HHS / United States