A protein, which function was unknown until now, has a vital role in the development of lung cancer. The finding, published in Oncogene, opens the door to the development of new antitumor strategies.

Researchers at the University of Granada (UGR) discovered how a protein called placofilin-1 (PKP1) works promoting lung cancer development. Until now, while the functions of this protein in the skin are well known, the role of placofilin-1 in cancer development was poorly understood.

The importance of desmosomes is well known because people who have these structures altered have severe skin problems. In fact, people with PKP1 mutations develop a disease called simple bullous epidermolysis, characterized by having very sensitive skin and suffering erosions and blisters extremely easy. PKP1 forms part of structures called desmosomes, which serve to provide resistance and cohesion of the skin.

Usually, this disorder manifests during childhood or the first years of life. Simple bullous epidermolysis enters into the so-called rare diseases, because it is uncommon and have no known cure, only palliative therapy can be applied.

It was completely unknown why this protein, which has an important function in the skin, increased its levels in lung cancer,” says Pedro P. Medina Vico, researcher at the UGR Department of Biochemistry and Molecular Biology I and leader of the research conducted at the Pfizer-University of Granada-Andalusia Board Center of Genomics and Oncology Research (GENYO).

First of all, we observed that PKP1 was one of the proteins that most increased its levels in lung cancer patients. And it was strange to see that a protein of the skin was expressed in lung tumors,” says Laura Boyero Corral, one of the lead authors of the study.

But it was also a mystery why a protein that helps keep cells together increases their levels in tumor processes, which tend to acquire precisely dispersal strategies, to generate what is called metastasis,” says Joel Martín Padrón, another of the authors of the study.

New antitumor strategies

This study opens the door to the development of new antitumor strategies. It has long been known that inhibition of MYC activity, a gene that promotes the development of tumors, could be important as cancer therapy. However, attempts to find MYC inhibitors have had little success so far, by the nature of this molecule.

We have shown that the cells that present the PKP1 product produce tumors in preclinical models, and when we eliminate this gene through the novel techniques of gene editing (CRISPR-Cas), the cells are unable to produce tumors, so the inhibition of PKP1 could be useful as a cancer therapy,” says Pedro Medina.

After analyzing our results and what was known so far about PKP1, we thought that it could be regulating the activity of MYC, which product is well known in cancer, since it acts by reprogramming the machinery of the cell to develop tumors. Immediately, we designed a series of experiments to test this hypothesis. When we obtained the results of such experiments, we clearly concluded that this was the case,” Medina concludes.

 

Source: SINC