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Collagen-rich omentum is a premetastatic niche for integrin a2-mediated peritoneal metastasis

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Resumo:The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.
Autores principais:Huang, YL
Outros Autores:Liang, CY; Ritz, D; Coelho, R; Septiadi, D; Estermann, M; Cumin, C; Rimmer, N; Schötzau, A; López, MN; Fedier, A; Konantz, M; Vlajnic, T; Calabrese, D; Lengerke, C; David, L; Rothen-Rutishauser, B; Jacob, F; Heinzelmann-Schwarz, V
Assunto:Cell adhesion Collagen Peritoneal metastasis Cancer biology Cell biology Focal adhesion kinase Human Integrin alpah 2 Mouse Omentum Zebrafish
Ano:2020
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Porto
Idioma:inglês
Origem:Repositório Aberto da Universidade do Porto

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