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.

Cells can use chemical modifications in chromatin to regulate accessibility to DNA to the repair complexes and to prevent transcription in case of damage. We analyzed the relationship between repair systems and epigenetic mechanisms in DNA and RNA. We searched the PubMed database for genes involved in DNA damage response (DDR) and methylation in mRNA and DNA repair, in cancer. Epigenetic modifications, particularly histone modifications and nucleosome remodeling, trigger a signaling cascade of kinases in DNA damage response (DDR) toward efficient repair. SWI/SNF remodelers promote the recruitment of repair factors in DNA, such as DNA double-strand breaks (DSBs) that activate kinases in DDR. RNA methylation via m6A has recently attracted attention as a possible alternative pathway for repairing DNA damage. m6A is a dynamic methylation mark on mRNA that accumulates after UV irradiation and regulates transcription to facilitate DNA repair. Currently, studies seek to understand how signaling pathways activate proteins in the early response to damage. The repair maintains DNA integrity, which is a challenge in cancer because this process also represents a potential barrier to anticancer agents. The impact that epigenetic regulation can have on DNA repair is beginning to be understood.

El concepto de epigenética emerge del concepto “epigénesis” propuesto en la década de 1940 por Waddington. Actualmente, se considera a la epigenética como la rama de la biología que estudia la modulación de la expresión del genotipo hacia un fenotipo particular o como el estudio de los cambios en la función genética que son heredables, pero no modifican la secuencia de nucleótidos en el DNA. Por otro lado, el epigenoma se refiere al conjunto de cambios epigenéticos a lo largo de todo el genoma. La modulación inadecuada en esta relación entre genes y factores epigenéticos también puede ser la causa del desarrollo o progresión de múltiples enfermedades. Este capítulo trata de manera introductoria: la metilación del DNA, modificaciones de las histonas, remodelación de la cromatina, el complejo SWI/SNF, así como los ácidos nucleicos circulantes y la epigenética.