Department of Molecular Cell Mechanisms Medical University of Lodz, 92215 Lodz, Poland.
Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 93338 Lodz, Poland.
Cells. 2019 Aug 1;8(8):810. doi: 10.3390/cells8080810.
Tumor metastasis, the major problem for clinical oncology in colon cancer treatment, is linked with an epithelial-mesenchymal transition (EMT). The observed cellular transformation in this process is manifested by cell elongation, enhanced cell migration and invasion ability, coordinated by cytoskeleton reorganization. In the present study, we examined the role of tubulin-β4 (TUBB4B) downregulation that occurs during EMT in colon cancer cells, in the modulation of the function of microtubules. Based on biochemical and behavioral analysis (transmigration) we posit that the decrease of the TUBB4B level is critical for microtubule-vimentin interaction and contributes to the maintenance of polarity in migrating cells. The microscopic studies revealed that TUBB4B decrease is accompanied by cell elongation and increased number of matured focal adhesion sites, which is a characteristic of the cell metastatic stage. We also demonstrated faster polymerization of microtubules in cells with a lower level of TUBB4B. Simultaneous TUBB3 upregulation, reported during EMT, acts additively in this process. Our studies suggest that the protein level of TUBB4B could be used as a marker for detection of the preinvasive stages of the colon cancer cells. We also concluded that chemotherapy enriched to increase TUBB4B level and/or to stabilize microtubule polymerization might more effectively prevent metastasis in colon cancer development.
肿瘤转移是结肠癌治疗中临床肿瘤学的主要问题，与上皮-间充质转化（EMT）有关。在这个过程中观察到的细胞转化表现为细胞伸长、增强的细胞迁移和侵袭能力，这是由细胞骨架重组协调的。在本研究中，我们研究了 EMT 期间发生的微管结合蛋白-β4（TUBB4B）下调在结肠癌细胞中的作用，及其对微管功能的调节作用。基于生化和行为分析（迁移），我们假设 TUBB4B 水平的降低对于微管-波形蛋白相互作用至关重要，并有助于维持迁移细胞的极性。显微镜研究表明，TUBB4B 的减少伴随着细胞伸长和成熟粘着斑数量的增加，这是细胞转移阶段的特征。我们还证明了 TUBB4B 水平较低的细胞中微管的聚合速度更快。同时，EMT 期间报道的 TUBB3 上调在此过程中具有加性作用。我们的研究表明，TUBB4B 的蛋白水平可以用作检测结肠癌细胞侵袭前阶段的标志物。我们还得出结论，化疗富集以增加 TUBB4B 水平和/或稳定微管聚合可能更有效地预防结肠癌发展中的转移。
