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Formation of tumor cell adhesion and following extravasation are limiting steps in organ specific metastasis. Focal Adhesion Kinase (FAK) plays a pivotal role in the intracellular signaling during cell adhesion and migration, which can be modulated by shear forces acting on circulating tumor cells. The intrinsic FAK inhibitor FRNK (FAK-related-non-kinase) was overexpressed in HEP G2 and HT-29 cells to investigate the role of FAK during early steps of metastasis. Static adhesion was not influenced by FRNK expression, whereas dynamic adhesion under flow conditions was dramatically reduced, apparent by significant reduced dynamic adhesion rates DAR (FRNK+: 12 ± 9 cells vs. FRNK-: 32 ± 10 cells; p 80%, p < 0.001) and complete inhibition of migration of the cells to the parenchyma. Our results indicate that FAK is involved in stabilization of cell adhesion on extracellular matrix in vitro and in vivo, which allows circulating tumor cells to resist the shear forces. This kinase is therefore involved in the regulation of rate limiting steps in distant metastasis formation.