New research suggests that the protein keratin 17 - the presence of which is used in the lab to detect and stage various types of cancers - is not just a biomarker for the disease, but may play a critical role in tumor growth. This new understanding of how keratin 17 works, the researchers say, could lead to the development of better ways to detect and prevent cancer, and identify new targets for therapeutic treatment. A report on the findings is published in Nature Genetics.
Keratin 17 is found in healthy hair follicles, fingernails and glands, but not in healthy epidermis, the outermost layer of the skin. It emerges, however, in basal cell skin cancers and most squamous cell cancer, and its appearance in such settings precedes the actual onset of tumor growth. Other researchers have determined that the quantity of keratin 17 present in other types of tumors such as in the breast, cervix, lung and pancreas can indicate how aggressive it is and help determine a patient's prognosis.
The researchers say keratin 17 doesn't cause the cancer itself, but promotes an inflammatory and immune response that can allow the disease to develop more aggressively.
For their study, the researchers worked with mice genetically engineered to develop skin cancer, in this case viral HPV-induced squamous cell carcinoma, building on their prior research in basal cell carcinoma, the most common form of skin cancer. When the researchers examined these models in the complete absence of keratin 17, the onset of the expected tumors was significantly delayed, correlating with a significantly dampened inflammatory and immune response. Importantly, the researchers were able to repeat the experiment in human tumor cells with a similar result.
Analyzing both mouse and human samples, the researchers determined that keratin 17 can move to the nucleus of tumor cells, and cause specific tumor-promoting inflammatory and immune response genes to be turned on.
The researchers also found that a protein called Aire (autoimmune regulator) interacts with keratin 17 in the nucleus of tumor skin cells. This represents yet another unexpected finding, as Aire is known to be a key player in the thymus, where it is essential in preventing the host's immune system from attacking itself. When the Aire gene was deleted, tumor formation was also delayed in mouse skin.
The ability to delay tumor formation could buy the necessary time for either the immune system to do its job and prevent tumors from growing or for anti-cancer medications to fight tumors that do form.
"A better understanding of what drives the onset, growth and characteristics of tumors will ultimately help us develop better biomarkers and treatments," the researchers concluded.
Based on material originally posted by Johns Hopkins University Bloomberg School of Public Health.