Investigation of cytoskeletal dynamics in IL-1β-induced epithelial-mesenchymal transition in breast cancer

The presence of interleukin (IL)-1β, a proinflammatory cytokine, has been demonstrated in the breast cancer microenvironment. IL-1β supports cell survival, proliferation, adhesion, invasion, and migration mechanisms. It also contributes to the chronicity and persistence of inflammation, therefore promotes cancer progression and epithelial-mesenchymal transformation (EMT). It is important for cells to gain mobility for EMT and metastasis. Cell movement is accomplished by the expression and functional interaction of skeletal elements. In addition to conventional cytoskeletal elements such as actin, vinculin, vimentin, Capping protein regulatory, ARp2/3, MyosinILinker (CARMIL) proteins are also involved in the regulation of the cell's actin skeleton. It can be said that CARMIL proteins are essential for cell motility and therefore EMT and metastasis. In the light of this information, a hypothesis was developed that IL-1β-induced EMT in breast cancer cells might be affected by CARMIL protein level and cellular distribution. The human breast cancer MCF-7 cell line owns epithelial morphology and MDA-MB-231 possesses mesenchymal morphology. To mimic the tumor microenvironment, these cells were grown on surfaces previously coated with MatrigelTM or fibronectin and treated with IL-1β to induce EMT. Obtained results were analyzed by immunofluorescent staining and qRT-PCR methods. It was observed that the expression levels of CARMIL3 and vinculin within the cells changed depending on the mesenchymal cell character. Evidence has been obtained that increased CARMIL3 mRNA levels may be a marker of early metastasis or partial EMT status in breast cancer. In conclusion, in this study, observations were made about the relationship of CARMIL proteins with cell mesenchymal character in IL-1β-induced EMT and the effect of IL-1β-mediated inflammatory responses on cancer progression.