Cancer linked to loss of protein that hooks skin cells together

WASHINGTON - A new study has found that the lack of a protein important in hooking our skin cells together could be an early indicator of skin cancer development.

Researchers at the Stanford University School of Medicine have said that the depletion of this protein, called Perp, could also be useful for staging and establishing prognoses.

Perp could also be a useful tool for classifying tumours in these internal organs, which are often diagnosed too late to be effectively treated.

Attardi first identified perp in the late 1990s. In 2005, in a study published in Cell, Attardi first showed that Perp is integral to desmosomes.

She and her associates produced mice lacking Perp, allowing them, unexpectedly, to identify a role that Perp plays in the skin.

“In this new study, we attempted to mimic the way skin cancers originate in people,” said Attardi.

She and colleagues exposed both normal mice and the bioengineered Perp-deficient mice to UVB light-a range of ultraviolet wavelengths known to induce the great majority of human skin cancers-and compared the incidence of squamous-cell carcinoma in the two groups.

In the mice lacking Perp, skin tumors arose faster, and were both more abundant and aggressive, than in normal mice.

“Perp loss promotes cancer in three different ways,” said Attardi.

The scientists observed the overproduction of inflammatory molecules (known to promote cancer), the increased survival of cells that should have committed suicide in response to excessive UVB and a loss of cell-cell adhesion commensurate with the loss of desmosomes.

At the same time, the mice with early stages of skin cancer continued to retain normal function of another variety of adhesion junction complex that has been observed to be dysfunctional in advanced cancer stages, such as metastasis.

The investigators also observed a substantial disappearance of Perp in biopsied human squamous-cell carcinoma samples.

Once again, the alternative adhesion junction complexes that have been implicated in later stages of cancer appeared to be present and functioning normally in almost all of these samples, further supporting the idea that desmosome loss due to Perp inactivation can be an early, defining event in cancer progression.

The study was published in the journal PLoS Genetics. (ANI)