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

Tiantian Wu*, Shanshan Xiong, Mimi Chen, Bjorn T. Tam, Wei Chen, Ke Dong, Zhenling Ma, Zhe Wang*, Gaoliang Ouyang*

*Corresponding author for this work

    Research output: Contribution to journalJournal articlepeer-review

    3 Citations (Scopus)

    Abstract

    Matrix 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.

    Original languageEnglish
    Pages (from-to)22-40
    Number of pages19
    JournalMatrix Biology
    Volume121
    Early online date23 May 2023
    DOIs
    Publication statusPublished - Aug 2023

    Scopus Subject Areas

    • Cell Biology
    • Physiology (medical)
    • Oncology

    User-Defined Keywords

    • Periostin
    • Matrix stiffness
    • Collective invasion
    • YAP
    • Breast cancer

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