PIEZO1 and neoplasm: Interestingly, the PIEZO1 gene, coding a mechano-sensitive sensor membrane-channel protein also locates in the endothelial/CAF-rich left region of spot E. The mechano-sensitivity of tumor and of TME-cells such as macrophages is important for their ability to transduce mechanical forces into biochemical signals associated with signaling pathways involved in cancer metastasis and EMT, such as angiogenesis, cell migration, intravasation, and proliferation [83,84,85], as well as cytokinesis and endosome trafficking [86].