Abstract
Epigenetic has become, in recent years, in a very important process in the control of several pathologies, including cancer. DNA methylation has been described in numerous studies as crucial for differentiation control, cell proliferation and invasion in cancer. Pancreas ductal adenocarcinoma is one of the most deadly diseases of our society; its complexity and variability have become one of the medical challenges of this decade. Combining the potential of epigenetic with the high mortality and the limited knowledge of pancreatic ductal adenocarcinoma origin, may result in new approaches for diagnosis, treatment and monitoring, crucial in this pathology. For this purpose, we analyzed genes involved in different cellular processes (GSTP1, p16, RASFF1A, RARβ2, CyclinD2, HIN-1, SOCS1, TIMP3, DAPK and TWIST1) in 61 cases of pancreatic ductal adenocarcinoma. A first approach led us to analyze the Src pathway, never studied in this sense, as crucial in the development of this pathology. Clusters for clinicopathological characteristics and epigenetic profiles were obtained. The high degree of methylation of these adenocarcinomas, and the statistical relationship between Src pathway methylation and clinicopathological profile, has been postulated, for the first time. These results show the importance of this pathway in pancreatic disease, opening a new challenge for research and therapy.
Highlights
Cancer is a complex disease characterized by multiple genetic and epigenetic genomic alterations [1,2]
Promoter regions are usually enriched with CpG dinucleotides, known as CpG islands; hypermethylation of these islands correlates with transcriptional silencing of tumor suppressor genes
In this study we analyzed epigenetic alterations in crucial pathways, mainly those derived from Src, in order to demonstrate the important role of epigenetic control and src pathway in pancreatic cancer development
Summary
Cancer is a complex disease characterized by multiple genetic and epigenetic genomic alterations [1,2]. Accumulating evidence demonstrates that cancer is associated with aberrant DNA methylation [2]. Src family nonreceptor protein tyrosine kinases transduce signals that control normal cellular processes such cell proliferation, adhesion and motility. Accumulating evidence implicates src as an important determinant of tumorogenesis, invasion, and metastasis. All these observations link src to multiple processes that determine the clinical outcome of a tumor, becoming a promising target for drug discovery and targeting. Overexpression of activated c-src has been reported to stimulate proliferation, cell migration and down-regulate E-cadherin expression in human pancreatic adenocarcinomas cell lines [7]. In this study we analyzed epigenetic alterations in crucial pathways, mainly those derived from Src, in order to demonstrate the important role of epigenetic control and src pathway in pancreatic cancer development
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
