Höhne Mila Y, Milani Wiebke, Ramlow Kirsten, Bogdan Sven
Department of Molecular Cell Physiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg 35037, Germany.
Proc Natl Acad Sci U S A. 2025 Jun 10;122(23):e2426702122. doi: 10.1073/pnas.2426702122. Epub 2025 Jun 4.
Collective cell migration is a key driver of tissue morphogenesis and cancer invasion. Here, we identified the tumor suppressor Ras association domain-containing protein 8 (RASSF8) as a WAVE interactor required for border cell migration. RASSF8 colocalizes with F-actin and cell adhesion molecules at border cell- border cell contacts. Loss of RASSF8 function results in border cell cohesion defects, a phenotype associated with changes in the localization of the Echinoid (Ed) and Coracle (Cora). Cell-type-specific RNA interference (RNAi) experiments suggest that cohesion defects are caused by changes in localization of Ed rather than E-cadherin. Gain-of-function experiments further revealed reciprocal functional interactions between RASSF8 and WAVE controlling collective border cell movement. Thus, we propose a dual function of RASSF8 in coordinating border cell cluster behavior. RASSF8 is thought to regulate the collective movement of border cells by restricting WAVE function, while it controls the epithelial cluster integrity by regulating cell-cell adhesion and septate junction molecules such as Ed and Cora.
集体细胞迁移是组织形态发生和癌症侵袭的关键驱动因素。在此，我们鉴定出肿瘤抑制因子含Ras关联结构域蛋白8（RASSF8）是边界细胞迁移所需的WAVE相互作用蛋白。RASSF8在边界细胞-边界细胞接触部位与F-肌动蛋白和细胞粘附分子共定位。RASSF8功能缺失导致边界细胞黏附缺陷，这一表型与类棘蛋白（Ed）和类皮质素（Cora）定位变化相关。细胞类型特异性RNA干扰（RNAi）实验表明，黏附缺陷是由Ed定位变化而非E-钙黏蛋白变化引起的。功能获得实验进一步揭示了RASSF8与WAVE之间在控制边界细胞集体运动方面的相互功能作用。因此，我们提出RASSF8在协调边界细胞簇行为方面具有双重功能。RASSF8被认为通过限制WAVE功能来调节边界细胞的集体运动，同时它通过调节细胞间黏附以及诸如Ed和Cora等分隔连接分子来控制上皮细胞簇的完整性。
