Regulation of tumor associated mechanosensors

   Cancer is a disease that dramatically changes the functional and mechanical properties of the original tissue. In the case of solid tumors, they tend to be much more rigid than the original tissue, and palpation of tissues has been used as a diagnostic approach to identify malignant growths. Therefore, signaling pathways that are regulated by mechanical parameters are frequently altered in cancer cells, contributing to the progression and spread of tumors (metastasis).

   Some of the most potent oncogenes, including c-Abl tyrosine kinase and YAP/TAZ transcriptional regulators are regulated by mechanical forces (Echarri et al., Nature Communications, 2019) and understanding this phenomenon is useful to design strategies oriented to prevent their activation. We have identified a mechanoresponsive pathway, led by the nuclear import factor Imp7, that is responsible for YAP/TAZ nuclear translocation (García-García et al., Nature communications, 2022), which provides a new opportunity to block YAP/TAZ function. Inhibition of YAP/TAZ is pursued by several pharmaceutical companies, due to the involvement of these factors in the progression of multiple tumors. In this research line, we aim to design new strategies to prevent the harmful effects of mechanoresponsive oncogenes, such as YAP/TAZ. In addition, we are developing new approaches to identify new mechanotransduction pathways important for tumor progression and metastasis.