A stiff fibrotic ECM, generated by fibroblasts and fibroblast-like cells, is also a major clinical hallmark of solid tumors, often associated with aberrant mechanotransduction (Paszek et al., 2005; Jaalouk and Lammerding, 2009; Calvo et al., 2013; Chronopoulos et al., 2016; Sarper et al., 2016), and this GPER-mediated mechanism may provide a therapeutic target wherein mechanical deactivation of fibroblasts leads to a reduction in tumor-permissive desmoplasia. The gene discussed is GPER1; the disease is neoplasm.