Tension mediates a glycocalyx-integrin feedback loop in cancer. The glycocalyx drives enhanced mechanical signaling between the integrin–actin axis on the tumor cell and the ECM. This mechanical signaling promotes the up-regulation of genes in the nucleus driving both a more mesenchymal phenotype (production of ECM proteins such as Tenascin C) and a bulkier glycocalyx (such as CD44, hyaluronic acid, and galectin-1) in the tumor. Together, these drive glioma aggressiveness in a tension-dependent feedback loop, which is self-enforcing. Illustration by Neil Smith (http://www.neilsmithillustration.co.uk).