Matrix Stiffening Facilitates the Collective Invasion of Breast Cancer through the Periostin-Integrin Mechanotransduction Pathway

Matrix Biol. 2023 May 23:S0945-053X(23)00069-0. doi: 10.1016/j.matbio.2023.05.006. Online ahead of print.ABSTRACTMatrix rigidity is a critical contributor to tumor progression; however, whether and how matrix stiffness modulates the collective invasion of tumor cells remain unknown. Here we demonstrate that increased matrix stiffness activates YAP to promote the secretion of periostin (POSTN) in cancer-associated fibroblasts, which in turn augments the matrix rigidity of mammary glands and breast tumor tissues by facilitating collagen crosslinking. Moreover, decreased tissue stiffening resulted from the POSTN deficiency impairs peritoneal metastatic potential of orthotopic breast tumors. Increased matrix stiffness also promotes three-dimensional (3D) collective breast tumor cell invasion via multicellular cytoskeleton remodeling. POSTN triggers the integrin/FAK/ERK/Cdc42/Rac1 mechanotransduction pathway during 3D collective invasion of breast tumor. Clinically, high POSTN expression correlates with high collagen levels in breast tumors and cooperatively determines the metastatic recurrence potential in breast cancer patients. Collectively, these findings indicate that matrix rigidity promotes 3D collective invasion of breast tumor cells via the YAP-POSTN-integrin mechanotransduction signaling.PMID:37230256 | DOI:10.1016/j.matbio.2023.05.006

Source: Matrix Biology - May 25, 2023 Category: Molecular Biology Authors: Tiantian Wu Shanshan Xiong Mimi Chen Bjorn T Tam Wei Chen Ke Dong Zhenling Ma Zhe Wang Gaoliang Ouyang Source Type: research