Gene essential for metastatic cancer cell growth identified

A gene found to be critical in metastatic cancer cell growth, provides new insight into the targeted treatment of cancers.

Researchers from the Mass General Cancer Centre in Boston, Massachusetts, have identified the Gstt1 gene to be pivotal for cancer cells to metastasise and spread throughout the body.

'Our results point to potentially novel therapeutic avenues to specifically target metastatic cancer,' noted Professor Raul Mostoslavsky, senior author of the paper published in Nature Cell Biology and scientific director of the Kranz Family Centre for Cancer Research at the Mass General Cancer Centre.

The study initially compared gene expression in primary and metastatic tumours in mice with pancreatic cancer or breast cancer. Each gene was then individually silenced to determine the effect. The scientists reported that silencing Gstt1 stopped metastatic cancer cells from growing and spreading, however it had no effect on primary tumour cell growth.

The Gstt1 gene is responsible for encoding an enzyme that is part of the superfamily of proteins involved in protecting cells from toxins, and has previously had no known role in cancer metastasis.

To further validate their findings, the scientists silenced the Gstt1 gene in two metastatic-derived human pancreatic cancer cell lines, confirming a significant reduction in metastatic growth.

Investigating how the Gstt1 enzyme interacts with metastatic cancer cells, the study indicated that these cancer cells were modified to secrete fibronectin, a protein that is known to be important in cells attaching themselves to the extracellular matrix. This matrix plays an essential role in cell movement, and is critical in the progression of cancer, allowing cancer cells to travel around the body.

'Gstt1 alters the matrix surrounding the metastatic cells so they can grow in these foreign niches,' continued Professor Mostoslavsky. 'Our results could lead to new strategies for the treatment of metastatic disease. This would be especially impactful for pancreatic cancer, in which most patients present with metastases when initially diagnosed.'

Pancreatic cancer is extremely aggressive, often being diagnosed after it has metastasised due to the primary cancer growth not presenting any symptoms. These findings, showing that Gstt1 is upregulated in both mouse and human metastases and functions as a driver of metastases, allow a new therapeutic strategy to be explored in the ongoing research for treating aggressive metastatic cancers.