The body's defence mechanisms: Teamwork is key for cancer-fighting proteins

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A new study published in Nature Communications shows that a molecular symbiosis between BAP1 and ASXL2 proteins can suppress cancerous tumors.

The mechanisms that regulate our bodies and keep us healthy are complicated, involving critical molecular components that are still poorly understood. The prestigious journal Nature Communications has published recent research on this topic by a team led by Dr. El Bachir Affar, an associate professor in the Department of Medicine at the Université de Montréal's Faculty of Medicine and researcher at the Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, part of the CIUSSS de l’Est-de-l’Île-de-Montréal network. Their work highlighted the crucial role played by a very specific protein, known as BAP1, in preventing cancer from developing. This discovery was made in collaboration with several other teams, including one headed by the study's co-principal investigator, Dr. Marc Therrien, an associate professor in the Department of Pathology and Cell Biology at the Université de Montréal's Faculty of Medicine and researcher at the Institute for Research in Immunology and Cancer (IRIC). 

What does BAP1 do?

Decades of research have shown that each of our cells is like a factory employing thousands of workers (who are, in this case, active proteins with highly specific roles and clearly defined life spans). Inside each cell, proteins communicate with one another so they can carry out their respective functions in perfect harmony. Any disruption in the way they work could lead to serious illness such as cancer. BAP1 plays a key role in protecting cells against cancer development—but, like other proteins, this tumour-suppressor can stop working properly. In fact, BAP1 defects are seen in many types of cancer, including mesothelioma, melanoma and renal cell carcinoma. To give a concrete example, BAP1 malfunctions have been found in one half of patients suffering from mesothelioma, a particularly deadly form of cancer. Dr. Affar's team had previously shown that BAP1 needed partners to remain operational and effectively protect cells, but how the molecular mechanism worked was still unknown.

Using advanced scientific techniques, Dr. Affar's and Dr. Therrien's teams were able to gain a better understanding of certain tumour suppression mechanisms, revealing the molecular symbiosis between BAP1 and its partner ASXL2. This mutually beneficial relationship helps protect cells and, as a result, keep organs cancer-free.

An important mechanism

This research helps us understand how proteins work together and identifies flash points where breakdowns can lead to cancer. These insights could lead to new cancer diagnosis and treatment strategies, which could in turn significantly improve survival rates among patients with mesothelioma or other cancers. Understanding how communication failures between BAP1 and ASXL2 manifest at the molecular level could make personalized medicine possible.

About the CIUSSS de l'Est-de l'Île-de-Montréal

The Centre intégré universitaire de santé et de services sociaux de l'Est-de-l'Île-de-Montréal (CIUSSS-Est) includes Maisonneuve-Rosemont Hospital, Santa Cabrini Hospital, the Canadian-Polish Welfare Institute, the Institut universitaire en santé mentale de Montréal, and the Saint-Léonard, Saint-Michel, Pointe-de-l'Île, and Lucille-Teasdale Health and Social Service Centres (CSSSs). Affiliated with Université de Montréal, the CIUSSS-Est combines the missions of teaching, assessment, and research of doctors and health professionals with excellence in health care delivery.

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