New treatments for cervical cancer may result from the recent identification of a protein that has the potential to prevent the growth of cervical cancer cells.1 Preclinical data, collected over 5 years through human samples and mouse models, has found that the protein cystatin E/M can inhibit cellular inflammation, which is a major contributor to the growth of cervical cancer.
The inflammation associated with cervical cancer typically develops after a woman contracts the human papilloma virus (HPV) from a male partner; the virus can eventually lead to the development of cervical cancer. Environmental factors such as smoking also are closely associated with the disease. Cervical cancer is the second most common cause of cancer-related deaths in women. HPV is detected in 90% of cervical cancers, and HPV is the most common sexually transmitted disease.
The researchers, led by Eri Srivatsan, MD, a member of the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, discovered by cystatin E/M prevents NFkB from entering the nucleus of cervical cancer cells. NFkB regulates inflammation. Thus, cystatin E/M decreases inflammation and slows tumor growth.
“When key inhibitory mechanisms break down, cancer cells produce inflammation that helps fuel cancer cell growth,” said Dr Srivatsan, who is a professor in UCLA’s department of surgery. “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.”
This study compared 20,000 genes in 2 sets of cells lines; 50% expressed cystatin E/M and 50% did not. Also, 66 samples of normal and cancerous cervical tissue were analyzed to determine the molecular mechanism that inhibits cancer cell growth.
Next, the researchers plan to determine how cystatin E/M inhibits tumor cell growth in chemo-radiation–resistant breast cancers in human samples and animal models.
The research was supported by the VA Greater Los Angeles Healthcare System.
1. Soh H, Venkatesan N, Veena MS, et al. Cystatin E/M suppresses tumor cell growth through cytoplasmic retention of NF-κB. Mol. Cell Biol. 2016;36(12):1776-1792.