The role of alpha7nAChR signaling in mediating tumor resistance to cancer therapy

• Grant number: 22/06146-6
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): July 01, 2022
• Effective date (End): June 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Nilton José dos Santos
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Despite all the technical scientific advances in the field of Oncology recorded in recent years, Cancer is still a high incidence disease and the second leading cause of mortality worldwide. By 2030, the expected global burden is 21.4 million new Cancer cases and 13.2 million Cancer deaths. Lung and Breast Cancers make up the majority of Cancers in men and women, with the exception of non-melanoma skin tumors. This epidemiological scenario of the disease is due, at least in part, to its tissue heterogeneity, which is a major challenge for its specific and early diagnosis, followed by the reduced effectiveness of the treatment due to therapeutic resistance. Several mechanisms are known to be related to resistance to chemotherapy, such as the presence of tumor stem cells (CSC) and increased activity of important signaling pathways such as JAK2/STAT3. It is known that alpha7-type nicotinic acetylcholine receptors (±7nAChR), in addition to the ion channel, are also capable of activating the JAK2/STAT3 pathway and inhibiting inflammatory processes, as well as participating in the oncogenic process. Recent studies have shown ±7nAChR is differentially expressed in different tumor types and is related to cell malignancy. Taken together, the evidence points to the role of ±7nAChR in chemoresistance and cell survival, a fact that has been scarcely explored in Lung and Breast Cancer. Our hypothesis is that the increased expression of this receptor on tumor cells mediates exacerbated activation of JAK2/STAT3, inducing the CSC phenotype, with consequent development of chemoresistance and cell survival. Thus, the main objective of this project is to evaluate cellular processes associated with Cancer progression and chemoresistance that may be related to the modulation of ±7nAChR expression. Furthermore, we will seek to investigate the involvement of ±7nAChR in cell cycle arrest, apoptosis, cell proliferation and migration. (AU)