Regulation of Cell Adhesion and Collective Cell Migration by Hindsight and Its Human Homolog RREB1

Abstract

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.

A 3D model of ovarian cancer cell lines on peptide nanofiber scaffold to explore the cell–scaffold interaction and chemotherapeutic resistance of anticancer drugs

“…It is favorable for cell adhesion and differentiation. 23 Broadly, these studies are consistent with our data. So the 3D cell model developed in this study was a good representation of the primary tumor and likely to simulate the in vivo biological characteristics of ovarian cancer cells.…”

“…So the 3D cell culture model in this study offered a type of cell pattern to explore the topographical features at nanoscale comparable with the scale of the ECM components and the biological activities of tumorigenesis, metastasis, and colonization. 16,17,23,25,26 Chemotherapeutic assay of anticancer drugs…”

Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

“…To obtain even smaller clusters, we knocked down E-cadherin specifically in central nonmotile polar cells, which causes clusters to break apart (29). Compared with other methods that generate smaller border cell clusters (34,35), this method does not directly alter the migrating cells themselves, thus presumably minimally changing their properties, and the smaller clusters generated are able to migrate. We measured average speed and average cluster size from 10 UpdGal4, UASEcadRNAi movies ( Fig.…”

Collective cell migration in development

“…The border cells are epithelial-like in character and, similarly to the cells in the LLP, have an apical-basal polarity and make contact with a basal lamina. It is evident that cell-cell adhesion needs to be dynamically regulated during the migration of border cells, and that the control of cadherin-mediated adhesion is also crucial (Geisbrecht and Montell, 2002;Melani et al, 2008).…”