Banning Antje, Babuke Tanja, Kurrle Nina, Meister Melanie, Ruonala Mika O, Tikkanen Ritva
Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
Department of Medicine 2, Hematology/Oncology, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
Cells. 2018 Apr 7;7(4):28. doi: 10.3390/cells7040028.
Cell-matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell-matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.
细胞与基质的黏附以及细胞迁移是重要的生理过程，在癌症扩散中也起着主要作用。在培养的细胞中，基质黏附依赖于含整合素的接触，如黏着斑。浮舰蛋白-1和浮舰蛋白-2在癌症中经常过度表达，并与生存率低相关。我们之前的研究揭示了浮舰蛋白-2在细胞与基质黏附以及肌动蛋白细胞骨架调节中的作用。我们在此表明，在伤口愈合试验中，浮舰蛋白对细胞迁移很重要，并影响黏着斑的形态和动态。此外，浮舰蛋白可增强软琼脂中的非锚定依赖性生长。在没有浮舰蛋白，尤其是浮舰蛋白-2的情况下，黏着斑激酶和细胞外调节激酶的磷酸化会减少。浮舰蛋白与α-辅肌动蛋白相互作用，α-辅肌动蛋白是黏着斑动态变化的主要调节因子。这些发现对于理解癌症中浮舰蛋白过度表达如何影响细胞迁移，尤其是增强转移形成的分子机制很重要。
