The study, published in the journal Gastroenterology, has proved in human cancer cell lines that this protein is essential to the correct activity of the oncogenic protein KRAS, related to cancer start and development. The interaction between HNRNPA2B1 and the protein codified by the gene KRAS is a potential therapeutic target against pancreatic cancer, one of the tumours with a worse prognosis.
The study was led by Neus Agell, professor from the Department of Cell Biology, Immunology and Neurosciences of the Faculty of Medicine of UB and researcher at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS). The first author of the study is Carles Barceló, PhD Student at the former UB Department. Researchers from the Catalan Institute of Oncology (ICO), the Bellvitge Biomedical Research Institute (IDIBELL), the Spanish National Cancer Research Center (CNIO) and the Dana-Farber Cancer Institute of the Harvard Medical School (USA) participated in the study too.
Mutations of the KRAS gene occur in over 90% of pancreatic carcinomas. The gene helps the cell to interpret what is happening outside and indicates what actions must be done next, for instance to reproduce itself or to die. Oncogenic mutations of the gene occur mostly in pancreatic, colon and adenocarcinomas in the lung. So, it always signals cells to proliferate, independently of the information that comes from outside.
Scientists have unsuccessfully tried to inhibit KRAS during more than thirty year in order to stop tumour development. “The strategy applied by the research team is to know better how the cell regulates its activity and how KRAS acts; therefore, if we are not able to inhibit directly the action of oncogenic KRAS, we try to hamper its interaction with other proteins in order to avoid its action and influence on tumours”, explains Neus Agell.
Researchers, together with the Proteomics Unit of the Scientific and Technological Centres of the UB (CCiTUB), studied the proteins that interact with KRAS in cancer cells. Among candidate proteins, the protein HNRNPA2B1 was selected. The next step was to knock down the protein in two different cell lines of pancreatic ductal adenocarcinoma (PDAC) —the most common type of pancreatic cancer— in order to observe the effects on tumour growth. Down-regulation took place, first, in cancer cell lines than need mutated KRAS gene in order to develop —they are named KRAS-dependent cell lines— and, second, in cell lines where the tumour can develop without KRAS. “Silenced HNRNPA2B1 protein reduced cancer cell proliferation and growth and increased cell death, but only in KRAS-dependent cell lines”, points out Neus Agell.
In a search for potential therapeutic targets