Department of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
Department of Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
Int J Mol Sci. 2018 Dec 23;20(1):53. doi: 10.3390/ijms20010053.
Colon cancer, the second leading cause of cancer-related deaths in the world, is usually diagnosed in invasive stages. The interactions between cancer cells and cells located in their niche remain the crucial mechanism inducing tumor metastasis. The most important among those cells are cancer-associated fibroblasts (CAFs), the heterogeneous group of myofibroblasts transdifferentiated from numerous cells of different origin, including endothelium. The endothelial-to-mesenchymal transition (EndMT) is associated with modulation of cellular morphology, polarization and migration ability as a result of microtubule cytoskeleton reorganization. Here we reveal, for the first time, that invasive colon cancer cells regulate EndMT of endothelium via tubulin-β3 upregulation and its phosphorylation. Thus, we concluded that therapies based on inhibition of tubulin-β3 expression or phosphorylation, or blocking tubulin-β3's recruitment to the microtubules, together with anti-inflammatory chemotherapeutics, are promising means to treat advanced stages of colon cancer.
结肠癌是世界上第二大致癌相关死亡的原因，通常在侵袭阶段被诊断出来。癌细胞与位于其龛位的细胞之间的相互作用仍然是诱导肿瘤转移的关键机制。这些细胞中最重要的是癌相关成纤维细胞（CAFs），是一种从不同来源的多种细胞（包括内皮细胞）转分化而来的异质性肌成纤维细胞。内皮-间充质转化（EndMT）与细胞形态、极化和迁移能力的调节有关，这是微管细胞骨架重组的结果。在这里，我们首次揭示，侵袭性结肠癌细胞通过微管蛋白-β3 的上调及其磷酸化来调节内皮细胞的 EndMT。因此，我们得出结论，基于抑制微管蛋白-β3 表达或磷酸化的治疗方法，或阻止微管蛋白-β3 招募到微管上，以及抗炎化疗，是治疗结肠癌晚期的有前途的方法。
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