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

Manuel Nolasco-Quiroga; Marisol Rosas-Díaz; José Moreno; Ricardo Godínez-Aguilar; María José López-Ibarra; Patricia Piña-Sánchez; Isabel Alvarado-Cabrero; Gerardo Vázquez-Gómez; Leticia Rocha-Zavaleta; Diego Arenas-Aranda; Fabio Salamanca-Gómez

doi:10.3892/ol.2019.10147

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

Oncol Lett. 2019 Jun;17(6):4779-4786. doi: 10.3892/ol.2019.10147. Epub 2019 Mar 15.

Affiliations

¹ Laboratory of Molecular Genetics, Medical Research Unit, Mexican Social Security Institute, National Medical Center Century XXI, Hospital of Pediatrics, Mexico City 06720, Mexico.
² Multidisciplinary Academic Unit Reynosa-Aztlan Reynosa, Autonomous University of Tamaulipas, Tamaulipas 88740, Mexico.
³ Direction of Research, Hospital Juárez de México, Mexico City 07760, Mexico.
⁴ Medical Research Unit of Oncologic Diseases, Oncology Hospital, Mexico City 06720, Mexico.
⁵ Department of Anatomy-Pathology, Mexican Social Security Institute, National Medical Center Century XXI, Oncology Hospital, Mexico City 06720, Mexico.
⁶ Department of Genomic Medicine and Envornmental Toxicology, National University of Mexico, Mexico City 04510, Mexico.
⁷ Department of Molecular Biology and Biotechnology, National University of Mexico, Mexico City 04510, Mexico.
⁸ Medical Research Coordination, Mexican Social Security Institute, National Medical Center Century XXI, Mexico City 04510, Mexico.

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 FAK²⁸ 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.

Keywords: biomarkers; focal adhesion kinase; isoforms; mucinous; ovarian cancer; serous.