Connections Matter: Collaborative Study Stems from Department of Pathology and Laboratory Medicine Annual Research Day

June 28, 2024 by Katelyn Queen, PhD

Top: Yvonne Janssen-Heininger, PhD, Reem Aboushousha, PhD. Bottom: Hend Abdelhamid, PhD, Raul Mostoslavsky, MD, PhD, and Christina Ferrer, PhD

A collaborative study, recently published in Nature Cell Biology, found its origins at the Department of Pathology and Laboratory Medicine Annual Research Day. At the meeting, keynote speaker Raul Mostoslavsky, MD, PhD, was introduced to Yvonne Janssen-Heininger, PhD, and the redox biochemistry research her lab conducts. This introduction led to a collaborative study focused on understanding the biological mechanisms that drive cancer metastasis.

Metastatic disease (the spread of cancer cells from their primary origin to new sites) accounts for 90% of cancer-related deaths1. Certain cancers, such as pancreatic cancers, have often metastasized at the time of diagnosis, contributing to a low five-year survival rate. Little is understood about what drives this metastatic nature, making it challenging to treat these diseases. The collaborative study between Janssen-Heininger and Mostoslavsky identified a new driver of metastasis, the protein glutathione S-transferase theta (GSTT). GSTT carries a compound known as glutathione and transfers the compound to other target proteins, changing the function of the receiving protein. The research group found that in metastatic cancer cells GSTT specifically modifies the protein, fibronectin. Fibronectin is a component of cells’ extracellular matrix, which surrounds and structurally supports cells and plays an important role in cellular communication. GSTT modification of fibronectin causes a cascade effect resulting in pro-metastatic cellular characteristics. These findings provide insight into how metastasis is controlled and maintained in certain cancer cells. 

A collaborative study between Raul Mostoslavsky, MD, PhD, and Christina Ferrer, PhD, from the Broad Institute of Havard and MIT, this study was made possible by UVM Cancer Center members Reem Aboushousha, PhD, and Hend Abdelhamid, PhD, who conducted the biochemical studies showing that GSTT can directly modify fibronectin. Future collaborative studies will focus on the development of GSTT inhibitors that could be used to treat metastatic disease. 

Read more about the study “The glutathione S-transferase Gstt1 drives survival and dissemination in metastases” here

References:

1. Anderson, R. L. et al. A framework for the development of effective anti-metastatic agents. Nat. Rev. Clin. Oncol. 16, 185–204 (2019).