Abstract
The Epithelial to mesenchymal transition (EMT) is the process that drives epithelial tumor cells to acquire an invasive phenotype. The role of transforming growth factor-β1 (TGF-β1) in EMT is still debated. We used confocal laser scanning microscopy and scanning force spectroscopy to perform a morphomechanical analysis on epithelial breast cancer cells (MCF-7), comparing them before and after TGF-β1 exogenous stimulation (5 ng/mL for 48 h). After TGF-β1 treatment, loss of cell–cell adherence (mainly due to the reduction of E-cadherin expression of about 24%) and disaggregation of actin cortical fibers were observed in treated MCF-7. In addition, TGF-β1 induced an alteration of MCF-7 nuclei morphology as well as a decrease in the Young’s modulus, owing to a rearrangement that involved the cytoskeletal networks and the nuclear region. These relevant variations in morphological features and mechanical properties, elicited by TGF-β1, suggested an increased capacity of MCF-7 to migrate, which was confirmed by a wound healing assay. By means of our biophysical approach, we highlighted the malignant progression of breast cancer cells induced by TGF-β1 exposure. We are confirming TGF-β1’s role in EMT by means of morphomechanical evidence that could represent a turning point in understanding the molecular mechanisms involved in cancer progression.
Highlights
The epithelial to mesenchymal transition (EMT) is an essential multi-step morphogenetic process that plays a key role in embryonic development, the differentiation of multiple tissues/organs, and tissue repair; it is involved in tumor progression [1,2]
The effects of external stimulation of transforming growth factor-β1 (TGF-β1) were evaluated on MCF-7 cells by confocal laser scanning microscopy (CLSM) in order to understand its potential role in E-cadherin loss
After 48 h of incubation with 5 ng/mL of transforming growth factor (TGF)-β1, confocal images showed appreciable differences in MCF-7TGF-β1 compared to the control: as a matter of fact, the treated cells exhibited weaker cell–cell adhesions (Figure 1a,b)
Summary
The epithelial to mesenchymal transition (EMT) is an essential multi-step morphogenetic process that plays a key role in embryonic development, the differentiation of multiple tissues/organs, and tissue repair; it is involved in tumor progression [1,2]. When EMT starts, epithelial cells become tumoral, undergoing a critical loss of their typical polarity, which involves both apical and basal membranes. This phenomenon induces the acquisition of a mesenchymal phenotype that makes cells able to infiltrate surrounding tissues [3,4]. The transforming growth factor (TGF)-β cytokines play a key role in the regulation of the growth, development, and homeostasis of tissues [5,6], but their involvement in EMT has been recognized [7,8,9]. The intracellular domains of TβR1-2 transduce extracellular signals into intracellular
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