Tumor suppressor gene promotes some colorectal cancers
SPROUTY2, a gene known to stop tumors spreading to other parts of the body in many types of cancer, appears to play the opposite role in some forms of colorectal cancer. This was the finding of a study published in the journal Oncogene and led by the University of Missouri School of Medicine in Columbia, which may spur new treatments for colorectal cancer.Senior author Sharad Khare, an associate professor in the School’s Division of Gastroenterology and Hepatology, says: “The gene known as Sprouty2 has previously been shown to protect against metastasis, or the spreading of cancer to other parts of the body, in breast, prostate and liver cancer.”
But he and his colleagues have discovered that the same gene may, in some cases, actually promote metastasis. For more than 3 years, they have been studying Sprouty2 in cancer cells, in mice with cancer and in samples taken from human biopsies.
They have used different ways of looking at how the gene behaves at the molecular level and found it plays a different role in colorectal cancer to the one it plays in other cancers. For example, in some cancers, Sprouty2 blocks molecular pathways that would otherwise allow cancer cells to grow and spread to other parts of the body.
But, as they describe in their study, the researchers also found that in some colorectal cancers, Sprouty2 appears to boost the metastasis pathways. Prof. Khare believes this happens when the gene is up-regulated or supercharged. The main reason people die of colorectal cancer is because of tumor recurrence and spread to other organs.
One of the study’s findings shows that silencing Sprouty2 suppresses epithelial-to-mesenchymal transition (EMT) in cells. EMT is a transformation process where a cell undergoes biochemical changes and acquires the ability to migrate and become more invasive and resistant to programmed cell death, or apoptosis.
Sprouty2’s role in regulating EMT had not been investigated in colorectal cancer before, note the authors. Prof. Khare says their findings are an important step in improving what we know about tumor spread in colorectal cancer, but it is also important to note they only appear to be true of a subset of colorectal cancer patients. He concludes:
“We don’t yet know why this is the case, but we hope to determine if there is a correlation between the up-regulation of this gene and the life expectancy of patients with colorectal cancer. Future studies will help us understand who may be at risk, and ultimately, if personalized treatments can be planned to target this gene.” Overall, it is estimated that about 1 in 20 people will develop colorectal cancer at some point in their lives, with women at slightly lower risk than men.