Molecular exploration of cancer hallmarks in the AIP Interactome

The aryl hydrocarbon receptor-interacting protein (AIP) is a conserved cellular protein that regulates cell growth and survival through diverse protein-interactions. Long recognised as a pituitary tumor suppressor, emerging evidence is now linking AIP to cancer progression in colorectal, gastric, pancreatic and breast cancers. This dual capacity to act as both an oncoprotein and a tumor suppressor underscores the need to better understand AIP's underlying role in cancer biology, which is the overarching aim of the MECH-AIP project.

By using high-throughput techniques such as RNA sequencing and mass spectrometry-based proteomics, our recent findings have shown that AIP acts as a key scaffold in colorectal cancer cells, bringing together cellular machinery responsible for protein production and recycling. Rather than operating in isolation, AIP appears to stabilise specific cancer-promoting proteins, effectively turning off a critical tumour-suppressing pathway while boosting signals that drive disease progression. These interactions highlight how AIP may help fuel cancer growth, offering a promising new clue to understanding cancer progression.

Although our findings remain exploratory and require further experimental validation, a clear overarching pattern emerged whereby many of the prioritised candidate proteins identified through mass spectrometry as AIP interactors, prevent cell death and support proliferation. Moving forward, we will focus on their validation and expand our research to include other cancer sub-types, particularly of breast origin. Through this research we hope to ultimately identify distinct predictive biomarker/s within the AIP interactome that can potentially have a diagnostic value.

The project is led by Prof. Therese Hunter (Principal Investigator) and Prof. Gary J. Hunter, from the Department of Physiology and Biochemistry, Faculty of Medicine & Surgery, University of Malta, with Dr Marita Vella and Ms Elena Ilia employed as researchers on the project. PhD candidate, Ms Abigail Dalli is also involved in the project. Additionally, two BSc (Hons) Medical Biochemistry undergraduate students (Ms Shanise Cachia and Mr Julian Coppini) also contributed to this research as part of their dissertation projects.

MECH-AIP is funded by the Cancer Research and Innovation Hub Malta (CRIHM) through the Cancer Research Programme 2024 Call managed by XJENZA Malta. Preliminary findings from this project have been disseminated across both local and international platforms, including the IX Malta Medical School Conference, the UM Research EXPO and the 4th MOSBRI Scientific Meeting held at the Louis Pasteur Institute in Paris.