Huang Sui, Ingber Donald E
Harvard Medical School and Children's Hospital, Boston, Massachusetts 02115, USA.
Cancer Cell. 2005 Sep;8(3):175-6. doi: 10.1016/j.ccr.2005.08.009.
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.
肿瘤学家常常根据触诊感觉到的组织硬度变化来诊断癌症,然而癌症研究人员通常关注的是生化信号传导机制。肿瘤更坚硬是因为它们具有更硬的细胞外基质。一项新的研究表明,这种基质力学的改变会激活整合素,整合素不仅通过细胞外调节蛋白激酶(Erk)促进有丝分裂信号传导,还通过Rho促进细胞收缩,这会进一步增加基质硬度。这建立了一个正反馈回路,开启乳腺上皮细胞的恶性表型。这种机械性“自分泌回路”使固态机械转导在恶性转化中与致癌信号通路处于同等重要的地位。