Wieczorek Katarzyna, Wiktorska Magdalena, Sacewicz-Hofman Izabela, Boncela Joanna, Lewiński Andrzej, Kowalska M Anna, Niewiarowska Jolanta
Department of Molecular Cell Mechanisms, Medical University of Lodz, Lodz, Poland; Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland.
Department of Molecular Cell Mechanisms, Medical University of Lodz, Lodz, Poland.
Exp Cell Res. 2017 Oct 1;359(1):163-170. doi: 10.1016/j.yexcr.2017.07.035. Epub 2017 Aug 1.
Filamin A (FLNA) is actin filament cross-linking protein involved in cancer progression. Its importance in regulating cell motility is directly related to the epithelial to mesenchymal transition (EMT) of tumor cells. However, little is known about the mechanism of action of FLNA at this early stage of cancer invasion. Using immunochemical methods, we evaluated the levels and localization of FLNA, pFLNA[Ser2152], β1 integrin, pβ1 integrin[Thr788/9], FAK, pFAK[Y379], and talin in stably transfected HT29 adenocarcinoma cells overexpressing Snail and looked for the effect of Snail in adhesion and migration assays on fibronectin-coated surfaces before and after FLNA silencing. Our findings indicate that FLNA upregulation correlates with Snail-induced EMT in colorectal carcinoma. FLNA localizes in the cytoplasm and at the sites of focal adhesion (FA) of invasive cells. Silencing of FLNA inhibits Snail-induced cell adhesion, reduces the size of FA sites, induces the relocalization of talin from the cytoplasm to the membrane area and augments cell migratory properties. Our findings suggest that FLNA may not act as a classic integrin inhibitor in invasive carcinoma cells, but is involved in other pro-invasive pathways. FLNA upregulation, which correlates with cell metastatic properties, maybe an additional target for combination therapy in colorectal carcinoma tumor progression.
细丝蛋白A（FLNA）是一种参与癌症进展的肌动蛋白丝交联蛋白。其在调节细胞运动中的重要性与肿瘤细胞的上皮-间质转化（EMT）直接相关。然而，在癌症侵袭的早期阶段，关于FLNA的作用机制知之甚少。我们使用免疫化学方法，评估了稳定转染过表达Snail的HT29腺癌细胞中FLNA、pFLNA[Ser2152]、β1整合素、pβ1整合素[Thr788/9]、黏着斑激酶（FAK）、pFAK[Y379]和踝蛋白的水平及定位，并在FLNA沉默前后，在纤连蛋白包被的表面上的黏附及迁移实验中寻找Snail的作用效果。我们的研究结果表明，在结直肠癌中，FLNA的上调与Snail诱导的EMT相关。FLNA定位于侵袭性细胞的细胞质和黏着斑（FA）部位。FLNA的沉默抑制了Snail诱导的细胞黏附，减小了FA位点的大小，诱导踝蛋白从细胞质重新定位到膜区域，并增强了细胞的迁移特性。我们的研究结果表明，在侵袭性癌细胞中，FLNA可能不作为经典的整合素抑制剂起作用，而是参与其他促侵袭途径。与细胞转移特性相关的FLNA上调，可能是结直肠癌肿瘤进展联合治疗的另一个靶点。
