Many adults are plagued with hardened skin – calluses – on the soles of their feet and on the palms of their hands. Often considered unsightly, these hardened skin formations serve to protect the skin beneath the epidermis. But in some people, excess calluses may reveal the presence of malicious cancer.
The study focused on patients who suffer from a hereditary form of throat cancer known as tylosis. In particular, scientists at the University of Queen Mary London discovered that tylosis patients typically have extreme calluses on their feet. Whereas calluses on other healthy people result in minor discomfort, the hardened skin in people with tylosis can get so thick as to cause pain and require shaving off with razors.
The gene identified in tylosis is iRHOM2, which regulates the production of keratin – one of the most abundant proteins key in the makeup of hair, skin, and nails.
To better understand whether this gene may link calluses to throat cancer, the research team looked at people who had increased iRHOM2 expression. Indeed, high iRHOM2 is associated with high keratin levels and increased risks for esophageal cancer.
The team also created a knock-out mouse model of iRHOM2. These mice showed lower levels of keratin, and paws with thinner skins than their control counterparts.
"These findings highlight a novel and fundamental role for iRHOM2 in regulating the epithelial response to mechanical stress," the authors wrote. This is the first research to link iRHOM2 and keratin interaction, as highlighted in tylosis and callused feet.
The study may also broaden the understanding of other skin conditions, such as eczema, rosacea, psoriasis, and even melanoma. "As K16 is highly expressed in disease states such as epithelial cancers and inflammatory dermatoses, there may be a broader significance for the role of iRHOM2 in the pathophysiology of these disorders, which remains to be explored,” the authors concluded.
Of note, throat cancer is part of the classification of head and neck squamous cell carcinoma (HNSCC). This type of cancer is the sixth common cancer worldwide, including cancers of the tongue, tonsils, soft palate and pharynx. Each year there are nearly 650,000 new cases and 350,000 deaths.