Invasive cervical cancer will be diagnosed in nearly 13,000 American women this year. Although routine Pap screening has significantly decreased the incidence of cervical cancer, the disease remains the second most common cause of cancer-related deaths in women in the US. As such, more research to discover the biological mechanisms driving this cancer is crucial.
To this end, researchers at the University of California, Los Angeles (UCLA) have found a protein that
suppresses the growth of cervical cancer cells. They also fleshed out the mechanisms of tumor suppression in this protein, possibly providing new treatment option against the deadly disease.
Using human samples and mouse models of cervical cancer, the research team found that a protein known as cystatin E/M acts a tumor suppressor. That is, its presence decreases cell inflammation, a process that normally promotes tumor growth. Though researchers suspected cystatin E/M could inhibit cancer, the recent report highlights the pathway in which this happens.
As it turns out, cystatin E/M prevents cervical cancer cells from receiving another protein, known as NF-kB. Known formally as the nuclear factor kappa-light-chain-enhancer of activated B cells, NF-kB is involved in immune responses to stimuli like stress and infection. Abnormal regulation of NF-kB has been notably linked to cancer, autoimmune diseases, and other adverse health conditions. Thus, by preventing NF-kB from entering the cervical cancer cells, cystatin E/M slows the growth of the tumor cells.
"When key inhibitory mechanisms break down, cancer cells produce inflammation that helps fuel cancer cell growth," said Eri Srivatsan, professor at UCLA's department of surgery, and senior study author. "By identifying this protein, we have discovered a key regulator of this breakdown. This is the first time we have found that inhibition of the protein kinase by cystatin E/M plays a regulatory role in cell inflammation."
The team observed suppression of tumor growth in mice treated with an artificial gene construct that expressed cystatin E/M in abundance. This evidence confirmed the role of cystatin E/M gene as a tumor suppressor gene. In addition, the team also analyzed tissues obtained from tumors, and found an inverse relationship between cystatin E/M levels and NF-kB levels. This supports cystatin E/M as an inhibitor of NF-kB.
Future studies will focus on how cystatin E/M influences tumor suppression in cancer cells that are resistant to chemotherapy and radiation. In addition, it will be interesting to find out whether the same biological pathway is involved in other cancer types, such as breast and ovarian cancer. But perhaps the most exciting outcome from this study is the possibility of new drug targets for the treatment of cervical cancer.
Additional source:
Science Daily
