Expression of FAK-related non-kinase (FRNK) coincides with morphological change in the early stage of cell adhesion

Abstract

Focal adhesion kinase (FAK), a protein tyrosine kinase, has recently been suggested to play a role in signal transduction through integrins. In fact, FAK is involved in cell proliferation and cell motility by performing signal transduction through integrins. FAK-related non-kinase (FRNK) has been found to be an inhibitor of FAK. As the expression level of FRNK in the cell is very low, the study of FRNK has been preferentially performed by gene overexpression, up to the present, and the role of constitutive FRNK in cells remains unclear. We hypothesized that FRNK is involved in the adhesion of cells to the extracellular matrix (ECM) and investigated the expression of FRNK by time kinetic analysis shortly after cell seeding. We found that FRNK expression was significantly increased in the cells during the early stage of cell adhesion to the ECM. These data indicated that FRNK plays an important role in cell adhesion during the very early stages of cell culture.

S-1 mediates the inhibition of lymph node metastasis in oral cancer cells

“…The present finding that tumor cells with downregulated FAK activity also became less adherent to the ECM suggests that S-1 is involved in the regulation of FAK phosphorylation. S-1 may lead to downregulation of the expression of certain integrins (29). The results of the present study confirm that systemic administration of S-1 inhibits metastasis of human OSCC cells grafted in the tongue of athymic nude mice.…”

Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition

“…However, previously reported defects during early cell spreading upon FAK inhibition and cell attachment upon FRNK overexpression (Richardson and Parsons, 1996) were not observed here. This may be because cells were able to overcome those effects at the later time points investigated here, or because it is the scaffolding role of FAK that mediates cell spreading, supported by data showing that coexpression of Src or catalytically inactive FAK can rescue cell spreading defects (Richardson et al, 1997) and endogenous FRNK expression is increased during the early stages of cell attachment (Nagoshi et al, 2006), indicating that FAK catalytic activity does not regulate this process. However, we found that pY-binding proteins displayed increased dynamics in IACs upon FAK inhibition, indicating that altered adhesion signaling may be the result of altered dynamics of IAC components rather than changes to IAC composition.…”

Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK)

“…It can upregulate the expression of cyclin D1, a key promoter in cell cycle progression, which accelerates the transition from the G1 to S phase . Overexpression of FAK can facilitate the G1/S phase transition, and one study indicated that the injection of the FAK-related nonkinase (FRNK) mutant in cells suppressed cell proliferation and caused the G1/S phase cell cycle arrest . Moreover, FAK can promote cell cycle progression by activating the Ras-ERK signaling pathway and enhance cell proliferation by disturbing the p53-mediated cell cycle arrest …”