Focal adhesion kinase drives proliferation and invasion in gastrointestinal neuroendocrine tumours via modulation of transformative cell signalling and gene expression

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Introduction: Focal Adhesion Kinase (FAK) is a non-receptor protein kinase that localises in both the cytoplasm and nucleus, influencing cell function through its enzymatic and scaffold activities. Through its scaffold function, FAK modulates gene expression epigenetically. Gastrointestinal neuroendocrine tumours (GI-NETs) exhibit a relatively low mutation rate, supporting the hypothesis that these malignancies may be driven epigenetically. Recently, PROTAC (PROteolysis TArgeting Chimeras) technology has enabled selective inhibition and degradation of FAK, providing a novel approach to explore its role in GI-NETs.

Aim(s): This study investigates the role of FAK in GI-NETs, examining both its enzymatic and scaffold functions.

Materials and methods: GI-NETs cell lines (GOT1 and COLO320DM) were cultured in both 2D and 3D conditions. Cell viability was assessed using CellTiter-Glo, and colony formation was stained with crystal violet. Invasion assays were conducted with transwell inserts, protein expression was analysed by western blot, and gene expression was measured via qPCR. FAK inhibition was achieved with Protac-FAK and Y15, while Mocetinostat was used to inhibit histone deacetylases (HDACs).

Conference:

Presenting Author: Gagliano T

Authors: Toffoli L, Ditsiou A, Moschioni E, Hamm V, Gagliano T,

Keywords: FAK, GI-NET, Cell Signalling, Epigenetics,