Researchers Dispel Information Surrounding Cancer Protein

UCSD researchers made a discovery in cancer research that challenges current dominant principles regarding cancer-causing enzymes. Once widely believed to promote cancer, protein kinase C was found to play a role in suppressing tumor growth.

Originally, the PKC enzyme family was thought to progress cancer because of the enzymes’ relationship to phorbol esters, a type of plant-derived compound that can breed tumors if applied to skin. These tumors grow as a result of PKC being activated when phorbol esters bind to them as receptors, which was what misled the scientific community to believing they were cancer-causing agents that needed to be stopped.

“For three decades, researchers have sought to find new cancer therapies based on the idea that inhibiting or blocking PKC signals would hinder or halt tumor development,” Alexandra Newton, professor of pharmacology and the study’s principal investigator, told UCSD News Center. “But PKCs have remained an elusive chemotherapeutic target.”

PKCs are involved in multiple cancer-related processes, not only those that encourage the disease. Corina Antal, first author of the study and graduate student in the UCSD biomedical sciences program, explained that, on the contrary, a few of its functions actually fight against cancer.

“Generally, PKCs have a lot of functions in the cell. They mediate a lot of processes involved in cancer: cell migration, cell proliferation, invasion,” Antal said. “So we think that it’s possible that in different cancers, these enzymes inhibit different processes.”

In order to gain an unbiased understanding of PKCs’ role in cancer, Newton’s group decided to investigate gene mutations identified in human cancer cases that were believed to affect the normal function of PKCs in cells. For example, one mutated gene could be coded in such a way that instructs cells not to create any PKC at all, and if so, its effect on cancer tumors would be observed.

Eight percent of the 550 PKC mutations involved in human cancer were analyzed in live cells. Most were discovered to obstruct or completely eliminate regular PKC function in cells. Furthermore, the loss of PKC function resulted in enhanced tumor growth in the mice.

When Newton’s group corrected for the PKC-preventing mutated gene in a colon cancer cell line of mice, the growth of the tumors was reduced. This demonstrated that allowing PKCs to pursue their normal function in cells prevents cancer from growing.

Antal told the UCSD Guardian that cancer treatments should, therefore, focus on restoring PKC function instead of disrupting it or hindering the proteins that process them.

“I think that the main point that came out of this is that we shouldn’t try and use PKC inhibitors to treat cancer,” Antal said. “In fact we should try and find ways of activating it, but at the least we should not try inhibiting because [inhibiting its function] is detrimental in itself.”

Treatments to activate and restore PKC function would likely be difficult to develop through drugs or chemotherapy. Because many gene mutations do not allow for the activation of PKC function, one way to restore PKC function in cells would be to replace the mutated gene with a corrected gene.

“One could envision that gene therapy could be used for [restoring PKC function] if you replaced that mutant copy of the gene with a normal copy,” Antal said. “But that’s sort of down the line; we’re not quite able to do that in humans yet.”