Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is expressed in most human cell types (example: Epithelial cells, fibroblasts and endothelial), it serves a key role in the control of cell survival, proliferation and motility. The abnormal expression of FAK has been associated with poor prognosis in cancer, including ovarian cancer. However, although FAK isoforms with specific molecular and functional properties have been characterized, there are a limited number of published studies that examine FAK isoforms in ovarian cancer. The aim of the present study was to analyze the expression level of FAK and its isoforms in ovarian cancer. The expression of FAK kinase and focal adhesion targeting (FAT) domains was determined with immunohistochemistry in healthy ovary, and serous and mucinous cystadenoma, borderline tumor and carcinoma samples. Additionally, the expression of FAK and its isoforms were investigated in three ovarian cancer-derived cell lines with western blotting and reverse transcription-semi-quantitative polymerase chain reaction. An increased expression of FAK kinase domain was determined in serous tumor samples and was associated with advancement of the lesion. FAK kinase domain expression was moderate-to-low in mucinous tumor samples. The expression of the FAK FAT domain in tumor samples was reduced, compared with healthy ovary samples; however, the FAT domain was localized to the cellular nucleus. Expression of alternative transcripts FAK°, FAK 28,6 and FAK 28 was determined in all three cell lines investigated. In conclusion, FAK kinase and FAT domains are differentially expressed among ovarian tumor types. These results indicated the presence of at least two isoforms of FAK (FAK and the putative FAK-related non-kinase) in tumor tissue, which is supported by the cells producing at least three FAK alternative transcripts. These results may support the use of FAK and its isoforms as biomarkers for ovarian cancer.

Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis

“…As a result, targeting integrin-dependent downstream effectors may also provide a similar inhibitory effect as integrin inhibition to prevent cancer cell dissemination. Increased expression of FAK signaling proteins has been identified in omental metastases, which is linked to poor prognosis in EOC ( Nolasco-Quiroga et al, 2019 ; Sood et al, 2004 ). In agreement with previous findings that depletion of FAK also inhibits local invasion and metastasis in vivo ( Provenzano et al, 2008 ), we could demonstrate that FAK inhibitor Defactinib dramatically reduces cancer cell proliferation, spheroid formation, and mesothelial clearance.…”

A key axis of the N-WASP signaling pathway promotes distant metastasis in pancreatic cancer: LOXL2-FAK-N-WASP

“…FAK, which is crucial for FA turnover, inhibits ECM proteolysis. The speci c role of FAK in the regulation of invadopodia formation and function in cancer cells [16][17][18][19][20][21].…”