Researchers at UT Southwestern Medical Centre identified that cancer cells which lack a key protein may be more obtrusive and are more likely to seep through. Researchers provided a drug that may possibly fight certain types of tumor. Dr. Burstein who is a member of the research team invented years ago the COMMD family of proteins and its abilities. He also revealed that one of these proteins, COMMD1, inhibits NF-kB.
COMMD1 is known to be a key factor which activates genes involved in inflammation. It often helps cancer cells survive and it manages a protein called HIF which plays a role in the survival of cells in areas of low oxygen, a common feature of cancer. For example, aggravated HIF activity is linked with tumor growth, metastasis and poor clinical outgrowth for cancer patients.
“Further down the line we could create a drug that would bring COMMD1 protein levels back to normal, or even above normal, in the tumor to hopefully affect cancer cell invasion,” said Dr. Ezra Burstein, assistant professor of internal medicine and molecular biology and senior author of the study. “If the cancer cells already have started invading other organs maybe further invasion would be halted or even regressed.”
COMMD1 has dual role in managing both NF-KB and HIF. This made the researchers identify that COMMD1 might be inactivated or repressed in tumors and researchers supported their assumptions. They identified low amounts of protein in a variety of human cancers and lowered expression of COMMD1 was also linked with more obstructive cancers. Dr. Burstein shared that COMMD1 reduction in cancer cells lead to increased activity of NF-KB and HIF which made the cancer more confined.
“This is the first study that clearly links COMMD1 to human disease and substantiates what we would’ve expected based on the prior work we have done on this protein,” he said. “COMMD1 is yet another player in the very important and complicated cancer invasion process.” Dr. Burstein said.
Researchers reviewed 63 patients with endometrial cancer and it was revealed that patients who had lowest levels of COMMD1 had bad clinical outcomes. Using mice researchers identified that COMMD1 deficient cells were more obstructive when implanted and mouse melanoma cells were introduced by them. These cells produced an outburst of COMMD1 which were injected into healthy mice. These cells expressed that greater levels of COMMD1 the number of metastatic lung tumors drastically reduced and that metastatic potential of an obstructive cell line may be blocked by COMMD1.
Dr. Burstein, mention that the next step in this research would be to check thoroughly the changes occurring in the tumor environment. It may be responsible for lowering levels of COMMD1 in cancer cells.
The research appeared in the June issue of the Journal of Clinical Investigation.