Invasive Colon Cancer Cells Induce Transdifferentiation of Endothelium to Cancer-Associated Fibroblasts through Microtubules Enriched in Tubulin-ß3.

ABSTRACT

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-ß3 upregulation and its phosphorylation. Thus, we concluded that therapies based on inhibition of tubulin-ß3 expression or phosphorylation, or blocking tubulin-ß3's recruitment to the microtubules, together with anti-inflammatory chemotherapeutics, are promising means to treat advanced stages of colon cancer.