Expression of Nek4 and Nek6 containing point mutations of human cancer and analysis of functional alterations in in vitro assays and human tissue culture

• Grant number: 24/20986-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Letícia Ester dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/15126-9 - Two cell cycle regulatroy protein families: from functional studies to their use as novel diagnostic markers and therapeutic targets in cancer, AP.TEM

Abstract

Cancer is characterized by genomic alterations that promote deregulated cell proliferation and resistance to treatments. This study investigates the roles of the Nek4 and Nek6 kinases in lung and prostate cancer, respectively, through the functional analysis of point mutations detected in these contexts. Nek4 is involved in microtubule stability and the cellular stress response, while Nek6 regulates critical steps in the cell cycle. Mutations in both kinases have been associated with tumor progression and resistance to therapies. Activator and inactivator mutations will be generated in the kinase and regulatorydomains of Nek4 and Nek6. These variants will be evaluated in knockout and wild-type cells, complemented with the wild-type and mutant forms of the proteins. Biochemical and cellular assays will investigate the effects of these mutations on apoptosis, proliferation, cell cycle, metabolism, migration, and DNA damage response. The expected results should clarify the functional impact of mutations in Nek4 and Nek6, contributing to the identification of molecular mechanisms underlyingtumor progression and therapeutic resistance, as well as validating these kinases as potential targets for interventions. (AU)