Cell tension, matrix mechanics, and cancer development.
Oncologists often diagnose cancer based on a change of tissue stiffness sensed by palpation, yet cancer researchers generally focus on biochemical signaling mechanisms. Tumors are more rigid because they have a stiffer extracellular matrix. A new study shows that this alteration of matrix mechanics activates integrins, which not only promotes mitogenic signaling through Erk but also cell contractility through Rho, which can further increase matrix stiffness. This establishes a positive feedback loop that switches on the malignant phenotype in mammary epithelial cells. This mechanical "autocrine loop" brings solid-state mechanotransduction on a par with oncogenic signaling pathways in malignant transformation.
Huang
Sui
S
Harvard Medical School and Children's Hospital, Boston, Massachusetts 02115, USA.
Ingber
Donald E
DE
D048430:Cell Shape; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction; D013314:Stress, Mechanical