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Impact of low molecular weight protein tyrosine phosphatase inhibitor on stomach Cancer cell biology

Grant number: 21/13349-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2022
Effective date (End): December 31, 2023
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal Investigator:Carmen Veríssima Ferreira
Grantee:Letícia Maria de Oliveira Magalhães
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Stomach cancer is fifth in incidence and third in mortality worldwide. Patients are often diagnosed late, with fewer therapeutic options and poorer survival. In this scenario, low molecular weight protein tyrosine phosphatase (LMWPTP) emerges as a target to increase therapeutic efficacy, as it participates in a molecular network responsible for providing some advantages for tumor cells that contribute to the complexity of the disease: sustaining proliferative signaling, resisting cell death, deregulating cell energy, contributing to immune evasion and stimulating invasion and metastasis. Therefore, the aim of the project is to evaluate the action of LMWPTP inhibitor I, N,N-diethyl-4-(4-((3-(piperidin-1-yl) propyl) amino) quinoline-2-yl) benzamide, in the biology of stomach cancer cells (Kato III and 23132/87) regarding adhesion capacity, migration, and antioxidant response. Until recently, there was no inhibitor on the market for LMWPTP that had high specificity and effect in biological conditions. Therefore, most of the validation tests of LMWPTP as a pro-tumor were performed through gene silencing by interfering RNA and CRISPR cas9. However, with the development of this inhibitor, we believe that the biological characterization in different cell models will be crucial for the advancement of clinical trials aiming at anti-cancer applications. Specifically, we aim to show that the inhibitor is also efficient in gastric cancer, that it has a long-term effect and reverses the constitutive activation of mediators associated with survival, adhesion, and migration.(AU)

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