Pancreatic cancer metastasis is regulated by an eleven amino-acid sequence

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis with a 5-year survival rate less than 5% because of its ability to metastasise, its late detection and the lack of effective therapies. The Integrin αvβ6 is highly overexpressed in PDAC and correlates with poor prognosis. The integrin β6 subunit contains a unique C-terminal tail of 11 amino acids (aa) that regulates downstream signals, although the mechanism remains unclear. Here, using integrin β6-deficient cells lines, we have developed two PDAC mouse models overexpressing the full-length β6 and a mutant β6 lacking the C-terminal 11aa (αvΔβ6). In vitro, αvβ6 overexpression increased cell proliferation, migration and invasion in a 3D spheroid model. The elimination of the C-terminal 11aa decreased proliferation and totally impaired cell migration and invasion. αvΔβ6 cells also expressed reduced MMP’s in vitro. In vivo, orthotopic implantation of αvβ6 overexpressing cells showed decreased overall survival and more spontaneous metastasis compared to αvΔβ6 and αvβ6-null cells. Therefore, the C-terminal 11aa of the integrin β6 subunit regulates PDAC progression and metastasis.