**2.2 The role of FAK, a critical mediator of integrin signaling, in ovarian cancer**

As a key player in cell adhesion, motility, and integrin-mediated cell signaling, FAK plays an important role in invasiveness and drug resistance in ovarian cancer. A study by Sood *et al*. reported that FAK is overexpressed in a panel of ovarian cancer cell lines, including SKOV3, EG, and 222, as well as in tissue samples from patients with invasive epithelial ovarian cancer, as compared to normal human ovarian surface epithelial cells and benign ovarian tissue samples [41]. The study showed that the dephosphorylation of FAK by FAK-related nonkinase (FRNK), decreased the invasion and migration of ovarian cancer cells *in vitro*. To evaluate the role of FAK degradation in cisplatin-mediated apoptosis in a cisplatin-sensitive ovarian cancer cell line, Sasaki *et al*. [92] treated OV2008 cells with varying concentrations of cisplatin

(0–10 μM) then analyzed FAK expression in detached cells. Relative to the small number of cells that remained attached following cisplatin treatment, the detached cells expressed low levels of FAK and an increased accumulation of FAK cleavage fragments. Further, morphological investigations on detached cells showed incidence of apoptotic nuclear condensation and fragmentation after 12-hours of incubation with cisplatin. Therefore, the results of this study suggest that cisplatin causes apoptosis in OV2008 cells by caspase-3-mediated FAK cleavage and cell detachment, which can be inhibited by either synthetic or endogenous caspase-3 inhibitors. In another study assessing the mechanism of taxane-based chemotherapeutic agent-mediated apoptosis, Halder *et al*. [93] reported an increase in FAK cleavage and caspase-3 activity in docetaxel-sensitive parental SKOV3 and HeyA8 ovarian cancer cell lines in response to docetaxel treatment. Both FAK cleavage and caspase-3 activity remained unchanged in resistant ovarian cancer cell lines SKOV3-TR and HeyA8-MDR. Furthermore, inhibiting caspase-3 by the caspase blocker, DEVD-fmk, decreased docetaxel-mediated FAK cleavage and apoptosis in parental cells. Similarly, silencing FAK by siRNA transfection increased docetaxel effectiveness in both parental and resistant cell lines.
