Elucidating the role of ANKHD1 in mRNA translation in gastric cancer cells

• Grant number: 25/24581-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: March 08, 2026
• End date: January 07, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: João Agostinho Machado Neto
• Grantee: Bruna Oliveira de Almeida
• Supervisor: Ivan Topisirovic
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: McGill University, Canada
• Associated to the scholarship: 22/11038-8 - Investigation of ANKHD1-related signaling pathways and biological processes in Stomach Cancer, BP.DD

Abstract

The Ankyrin repeat and KH domain-containing protein 1 (ANKHD1) is a multidomain scaffold protein implicated in oncogenic signalling. ANKHD1 is able to mediate protein-protein and protein-nucleic acid interactions through its ankyrin repeats and KH domain, thus regulating diverse signalling networks. In gastric cancer cells, which display high ANKHD1 expression, preliminary results from immunoprecipitation followed by mass spectrometry analysis identified 69 candidate ANKHD1 interactors. These proteins were found to be significantly enriched for translation-related processes, including translation initiation factors, small ribosomal components, and regulators of P-bodies and stress granules. This finding suggests a novel role for ANKHD1 as a translational mediator. Therefore, the present project aims to deepen the understanding of the contribution of ANKHD1 to mRNA translation in gastric cancer by determining transcriptome-wide changes in translation after ANKHD1 depletion through polysome profiling and RNA sequencing, validating differential translation of candidate mRNAs by RT-qPCR and protein analysis, and investigating the involvement of ANKHD1 in P-body and stress granule assembly under basal and stress conditions. By integrating proteomic, transcriptomic, and cellular approaches, this study will provide the first comprehensive characterization of ANKHD1 in translational regulation. Altogether, the expected results of this proposal will clarify the ANKHD1 contribution to gastric cancer biology; moreover, they may reveal previously unrecognized mechanisms of translational control with therapeutic potential. (AU)