Invasion and metastasis is a hallmark of malignant tumor,in addition to the metastasis of distal target organs,there are also the invasions of surrounding tissues and lymph nodes.Besides single cell migration,Carcinomas typically invade as a cohesive multicellular unit,a process termed collective invasion.We developed three-dimensional(3D)organoid assays to prove that periostin transfered matrix mechanical signal to tumor cells,via binding to ?v?3 or ?v?5.Furthermore,POSTN triggers the FAK/ERK/Cdc42/Racl mechanotransduction pathway in breast tumor organoids,and promotes the collective invasion of breast cancer cells by rearrangement of actin cytoskeleton.In this process,the secretion of periostin was regulated by matrix stiffness,which in turn augments the matrix rigidity of tumor tissues by accelerating collagen crosslinking and extracellular matrix remodeling. |