Melanoma is a highly aggressive type of skin cancer produced by malignant transformation of melanocytes and it is usually associated with a poor prognosis. Clinically, melanoma has several stages associated with migration and invasion of the cells through the skin layers, rapid cell spreading and formation of tumors in multiple organs. The main problem is the emergence of resistance of melanoma to the applied methods of treatment, thus it is of primary importance to find more crucial signaling pathways that control the progression of this type of cancer and could be targeted to prevent melanoma spreading. The main life-threatening stage of melanoma is metastasis formation, and 3D cell spheroids are better suited for the study of this process. Using a combinative approach (RT-PCR, immunofluorescence, patch-clamp and calcium imaging) we showed the functional expression of mechanosensitive Piezo1 channels in SK-MEL-2 aggressive melanoma cell line. We found that chemical activation of Piezo1 by its selective agonist Yoda1 completely prevents melanoma spheroid formation, and could be considered as a novel approach for the prevention of melanoma development.

The rhythmical nature of the cardiovascular system constantly generates dynamic mechanical forces. At the center of this system is the heart which must detect these changes and adjust its performance accordingly. Mechano-electric feedback provides a rapid mechanism for detecting even subtle changes in the mechanical environment and transducing these signals into electrical responses which can adjust a variety of cardiac parameters such as heart rate and contractility. However, pathological conditions can disrupt this intricate mechanosensory system and manifest as potentially life-threatening cardiac arrhythmias. Mechanosensitive ion channels are thought to be the main proponents of mechano-electric feedback as they provide a rapid response to mechanical stimulation and can directly affect cardiac electrical activity. Here we demonstrate that the mechanosensitive ion channel Piezo1 is expressed in zebrafish cardiomyocytes. Furthermore, chemically prolonging Piezo1 activation in zebrafish results in cardiac arrhythmias indicating that this ion channel plays an important role in mechano-electric feedback. This also raises the possibility that Piezo1 gain of function mutations could be linked to heritable cardiac arrhythmias such as atrial fibrillation in humans.

TMEM16A is a Ca2+-activated Cl- channel expressed in various species and tissues. In mammalian skeletal muscle precursors, the activity of these channels is still poorly investigated. Here, we characterized TMEM16A channels and investigated if the pharmacological activation of Piezo1 channels could modulate the TMEM16A currents in mouse myogenic precursors. Whole-cell patch-clamp recordings combined with the pharmacological agents Ani9, T16inh-A01 and Yoda1 were used to characterize TMEM16A-mediated currents and the possible modulatory effect of Piezo1 activity on TMEM16A channels. Western blot analysis was also carried out to confirm the expression of TMEM16A and Piezo1 channel proteins. We found that TMEM16A channels were functionally expressed in fusion-competent mouse myogenic precursors. The pharmacological blockage of TMEM16A inhibited myocyte fusion into myotubes. Moreover, the specific Piezo1 antagonist Yoda1 positively regulated TMEM16A currents. The findings demonstrate, for the first time, a sarcolemmal TMEM16A channel activity and its involvement at the early stage of mammalian skeletal muscle differentiation. In addition, the results suggest a possible role of mechanosensitive Piezo1 channels in the modulation of TMEM16A currents.