p63 protein goes a long way in its development, and defects in p63 can lead to birth defects such as cleft palate, finger-joined fingers or even missing limbs. But as soon as its formation is completed, of p63 stops if you do not accidentally activated. Activation of p63 in the adult genome can lead to cancer. More than half of all squamous cell carcinomas are often found in the skin, lung, breast, and head / neck are associated with excessive activity of p63.
Researchers knew that p63 causes squamous cell carcinoma. The question is what to do. Unfortunately, it was impossible to simply turn off p63. And so the question arises as more doctors and researchers can intervene in the action of p63 to protect patients from its cancerous effects.
Today, a group of researchers from the University of Colorado Cancer Center, working in the lab Joaquin Espinosa, Ph.D., sheds light on p63 activity in squamous cell lung cancer, providing an effective way to the development of a drug against the known causes of cancer. The study is published in the journal Cell Reports.
"The question of who initiates this study - is that this oncogene, of p63, making in order to stimulate cell proliferation and why it can cause cancer," - says Espinosa.
To answer this question, Espinosa and his colleagues, including first author Christopher Abraham, PhD, used functional Genomics Resource Center CU genotypic cell to run through the CRISPR screen - cutting-edge technology that allows us to analyze thousands of genes in a single experiment. The group began with lung carcinoma cells of squamous cell carcinoma that needed oncogene product p63 gene, namely protein called Np63a, to breed. The group then turned off Np63a production in these cells.
Of course, at this point the cancer cells that are needed Np63a, ceased to apply. Espinosa and colleagues suggest that Np63a inhibits the action of key tumor suppressor genes (genes off, which cause cancer), and now without Np63a these key genes antiproliferative again allowed to take and stop cell division.
"This is a classic example of a tug of war between oncogenes and tumor suppressor genes, based on this balance, you either have cancer or not," - says Espinoza.
To identify these tumor suppressor genes that play tug of war with the help of Np63a, the group used CRISPR screen to disable thousands of genes throughout the genome to discover which genes when they are inactivated, allow these cancer cells to resume their growth (and thus , genes suppress ΔNp63α to help the growth of cancer).
"We conducted a genome-wide screening, and was one molecular pathway that Np63a had to disable, to stimulate the growth of cells of squamous cell carcinoma", - says Espinosa.
Key tumor suppressor genes in this pathway are TGFB2 and RHOA.
When the group looked into genome Atlas cancer with published data for 518 specimens of squamous cell carcinoma lung cancer, they found that when an activated cancer Np63a about 80 percent and exhibited inactivated and TGFB2 RHOA.
«Np63a disables TGFB2 RHOA and to promote the progression of cancer, and this is obviously a widespread phenomenon in the squamous cell carcinoma, - says Espinoza.
The path to the therapy against Np63a seems clear: activate and TGFB2 RHOA.
"So if you can find the medications that block RHOA in the active form, it also closes the cell proliferation", - says Espinosa.
"This is potentially a medicinal way that stimulates the development of squamous cell carcinoma", - says Espinoza. "Now the challenge is to use this knowledge for treatment, find a way to reactivate the way TGFB / RHOA to save the lives of patients with cancer."