The methylase SMYD3 promotes tumor cells proliferation, migration and invasion. It is over-expressed in breast cancer (BC), however, a detailed investigation of SMYD3 roles in different molecular subtypes of BC is still lacking.
A new role of SMYD3 in regulating homologous recombination (HR) DNA repair recently emerged. In particular, inhibition of SMYD3 directly blunts HR efficiency by downregulating the expression of HR-related genes, including BRCA2.
In the last years, interest on SMYD3 as prognostic marker and therapeutic target in various solid cancers increased, as great attention has been given to cancers associated with germline mutations in HR genes, due to the clinical relevance related to treatment selection.
In this project, we aim to evaluate SMYD3 expression in BCs characterized by BRCA1/2 mutation status and also to perform germline mutational analysis of SMYD3 gene in BC patients, both females and males, in order to provide insights on its role in BC susceptibility.
BC in men is a rare and less investigated disease compared with BC in women. Due to its rarity, male BC research and clinical management has been considered similar to female BC management. However, increasing molecular evidence indicate that BC in men and women may behave differently.
Overall, the findings of this research project, aiming to characterize SMYD3 as molecular biomarker in specific BC subgroups, will provide insight into the role of SMYD3 in the pathogenesis of BC and eventually into possible new prognostic and therapeutic approaches for BC patients of both genders.
The methylase SMYD3 promotes tumor cells proliferation, migration and invasion. Although it is known that SMYD3 is over-expressed in BC, a detailed investigation of its levels and roles in different molecular subtypes of BC is still lacking. For instance, little is known on SMYD3 expression levels and contribution to cancer development in BC patients carrying BRCA1/2 mutations. Moreover, it is still not clear if SMYD3 involvement in alterations of transcriptional regulation, protein signaling or DNA repair may play a role in different types of BC. Recently, interest on SMYD3 as a prognostic marker and a therapeutic target in various solid cancers has emerged, as great attention has been given to cancers associated with germline mutations in HR genes due to the clinical relevance related to treatment selection. In this regard, currently there are scarce data for BC.
In this project, we aim to evaluate SMYD3 expression in BCs characterized by BRCA1/2 mutation status and also to perform a germline mutational analysis of SMYD3 gene in BC patients, in order to provide insights into its role in BC susceptibility.
Taking advantage of our large series of male BCs, we will perform the study both on female and male BCs, thus adding information on the role of SMYD3 in BC from both genders. BC in men is a rare and less investigated disease compared with BC in women. Due to its rarity, male BC research and clinical management has been considered similar to female BC management. However, increasing molecular evidence indicate that BC in men and women may behave differently. Thus, there is a need to obtain further evidence on the genetics and biology of this rare disease and how to best treat and support male BC patients. On the other hand, because of its rarity and because it is not affected by confounding variables related to the reproductive history and high frequency, as female BC, male BC is an ideal model to improve knowledge of the biology and genetics of BC in general.
Overall, the findings of this research project, aiming to characterize SMYD3 as a molecular biomarker in specific BC subgroups, will provide insight into the role of SMYD3 in the pathogenesis of BC and eventually into possible new, individualized prognostic and therapeutic approaches for BC patients of both genders.