SUSD2 Promotes Metastasis and Primary Tumor Growth in Pancreatic Cancer Cells via Integrin–FAK Signaling Activation

Tumor tissues in pancreatic cancer develop with abundant cancer-associated fibroblasts (CAFs), promoting tumor progression. CAF-conditioned medium induces the expression of sushi domain-containing 2 (SUSD2) and enhances the invasive potential of pancreatic cancer cells. We showed that SUSD2 binds to integrin β1 and promotes pancreatic cancer cell motility by inducing phosphorylation of focal adhesion kinase (FAK), facilitating the formation of focal adhesion complexes in cells adhered to collagen 1 or fibronectin. Orthotopic transplantation of SUSD2-overexpressing human pancreatic cancer cell lines into the mouse pancreas enhanced liver metastasis in Panc-1 cells, whereas in KP2 cells, it increased primary tumor growth without promoting metastasis. In spheroid cultures of KP2 cells, forced SUSD2 expression elevated FAK phosphorylation independently of cell adhesion, suggesting that SUSD2 promotes cell proliferation even in non-metastatic cells. High SUSD2 expression in cancer cells contributes to tumor growth and metastasis, identifying SUSD2 as a potential therapeutic target in pancreatic cancer.