The role of transgelin (TAGLN) in cancer has been discussed; however, the mechanisms underlying its regulation and correlation with MDA‐MB‐231 cell plasticity and migratory patterns remain unclear. We generated stable TAGLN‐knockdown MDA‐MB‐231 cells and treated them with phorbol 12‐myristate 13‐acetate or transforming growth factor (TGF)‐β. Chemotaxis, morphology, and invasion were assayed using three‐dimensional matrices to evaluate cytoskeletal remodeling and migratory changes. Wound healing assays were conducted using cell inserts. TAGLN knockdown cells exhibited altered morphology due to cytoskeletal remodeling, yet only untreated and TGFβ1‐treated cells exhibited enhanced migration. Untreated and TGFβ1‐treated TAGLN knockdown cells showed increased N‐WASP, ROCK1, and ROCK2 protein levels, which induce cytoskeletal remodeling. Evaluating phospholipase Cγ1 (PLCγ1)‐cofilin signaling‐related proteins revealed that only TGFβ1‐treated TAGLN knockdown cells were influenced by PLCγ1‐cofilin signaling. Taken together, TAGLN knockdown is necessary for the TGFβ1‐mediated activation of PLCγ1‐cofilin pathway‐driven amoeboid morphology and enhanced migratory properties in MDA‐MB‐231 cells.
Signaling between cancer cells, their neighboring cells, and mesenchymal stem cells (MSCs) forms the tumor microenvironment. The complex heterogeneity of this microenvironment varies depending on the tumor type and its origins. However, most of the existing cancer-based studies have focused on cancer cells. In this study, we used a direct co-culture system (cross-talk signaling) to induce cross-interaction between cancer cells and mesenchymal stem cells. This induced deformation of MSCs. MSCs showed a diminished ability to maintain homeostasis. In particular, increase in the invasion ability of MSCs by TGF-β1 and decrease in p53, which plays a key role in cancer development, is an important discovery. It can thus be deduced that blocking these changes can effectively inhibit metastatic colorectal cancer. In conclusion, understanding the interactions and changes in MSCs associated with cancer will help develop novel therapeutic strategies for cancer.
Extremely low‐frequency electromagnetic fields (ELF‐EMFs) (1–300 Hz) have been found to have practical applications in biological research. A case in point is the effect of ELF‐EMF on the regulation of cell fate. In this study, we investigated the correlation between ELF‐EMF stimulation of PPARγ to the stemness, tumorigenicity, and invasiveness of breast cancer stem cells in vitro. The CD44+/CD24− subpopulation of the breast CSCs was isolated from the MDA‐MB‐231 breast cancer cell line. The CSCs were then exposed to ELF‐EMF and further assays were carried out. ELF‐EMF increased the expression of PPARγ and other critical proteins leading to cell cycle arrest and reduced stemness as evidenced by decreased expression of stemness genes and reduced proliferation rate in ELF‐EMF‐exposed CSCs compared to that in nonexposed CSCs. There was a decrease in the tumor‐forming and invasion ability of CSCs that were exposed to ELF‐EMFs.
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