New research in Neoplasia

New research from POI-funded researchers has highlighted important differences in the effect of saturated and unsaturated fats on different stages of disease progression in oesophageal adenocarcinoma.

Published recently in Neoplasia, the study entitled “(opens in a new window)Saturated fat exacerbates mitochondrial dysfunction through remodelling of ATP production and inflammation in Barrett’s oesophagus compared to monounsaturated fat, particularly in contrast to oesophageal adenocarcinoma” was led by POI-funded researchers Dr. Kathleen Mitchelson, Prof. Helen Roche and Prof. Jacintha O’Sullivan.

The study’s authors cultured two different cell lines representing oesophageal carcinoma and Barrett’s oesophagus (a non-cancerous precursor) with saturated and unsaturated fats. Saturated fats were found to induce an inflammatory response, especially in Barrett’s cells, suggesting that high intake of these fats could increase the likelihood of a patient with Barrett’s oesophagus progressing to a cancer diagnosis.

Lead-author Dr. Kathleen Mitchelson explained;

We were able to gain preliminary immunometabolic phenotyping on the different stages within oesophageal disease but warranted further exploration to fully elucidate specific mechanisms. “We wanted to extend previous research within the Nutrigenomics group led by Prof. Helen Roche into obesity-linked cancers to understand how saturated versus unsaturated fatty acids may differ in their contribution to oesophageal disease

This study represents a great example of the collaborative network grown through POI, with 2 POI-funded PIs working together, while also drawing on the POI Shared Resources Platform to access proteomics expertise within Systems Biology Ireland and UCD Conway Institute.

Study co-author and SBI Group Leader Dr. David Gomez Matallanas highlighted his role in the study;

This was a new area of research for our group, and the collaboration quickly expanded to research other aspects of not only oesophageal but also colorectal cancer. Importantly, as part of her PhD, Kathleen Mitchelson worked closely with Kieran Wynne (CMAP Infrastructure Manager) to apply and develop new methods that are the foundations for new collaborations between the O'Sullivan and Roche groups and several researchers in SBI.”

With obesity now overtaking smoking as the leading cause of cancer, gaining a deeper understanding of the precise relationship between diet and cancer development is crucial, as explained by senior author Prof. Helen Roche.

“Excess dietary energy leads to obesity, which is linked to some cancers, but not all fats are the same. Here we show saturates alter fatty acid metabolism, oncogenic signalling, mitochondrial protein-protein networks coincident with greater inflammation in the early pre-cancer state. In contrast unsaturated fatty acids are less problematic.”

This study not only brings important insights to a rapidly developing field of tumour biology, with potentially significant clinical relevance for patients with Barrett's oesophagus or oesophageal cancer,  but further underlines the importance of linking up multiple groups with different areas of expertise. As summarised by POI & SBI Director, Prof. Walter Kolch;

"We're delighted to see this important collaborative publication coming from labs in two different universities in the Precision Oncology Ireland consortium. Studies such as these resulting in key advances in personalised healthcare really show the success of the POI programme and the way in which it brings together our network of researchers with diverse expertise to answer some of the biggest challenges in modern medicine."