New therapies must target a key protein interaction to destroy aggressive cancer cellsf protective force field, University of Florida scientists reported in April at the American Association for Cancer Researchfs annual meeting in San Diego.
The barrier deflects damage from radiation or chemotherapy, making some cancer cells difficult to destroy, but researchers from UF and the University of North Carolina at Chapel Hill may have discovered why. Their study revealed that mutations in the tumor-suppressing p53 protein lead to overabundance of a second protein called focal adhesion kinase, or FAK, which makes the cells less vulnerable to attack.
gThese findings are significant to future cancer research and the development of new therapies,h said Vita Golubovskaya, an assistant professor in the UF Department of Surgery, who presented the findings. gThe high correlation between these two markers is critical for predicting patient prognosis.h
The next step will involve developing cancer therapies that target this interaction, Golubovskaya added.
Both p53 and FAK are found in low levels in normal, healthy cells. The p53 protein ensures that cells strike a wholesome balance between growth and death. In its normal state, p53 suppresses the FAK protein and weakens the molecular force field around cancer cells. But mutations in the p53 protein can interfere with this regulatory function.
Mutations in the p53 gene are commonly found in patients with cancer, and those with more aggressive forms of the disease boast particularly high levels of p53 and FAK. Most cancer therapies are largely ineffective against the resulting FAK force field, which has been identified in melanoma and most solid tumors of the breast, lung, brain, thyroid and colon.
Scientists are still unsure what causes mutations in p53 and why FAK binds to the damaged protein. But the study revealed that the interaction interferes with the signaling process that normally induces cell death, allowing cancer cells to grow unchecked.
The population-based study centered on 600 patients with breast cancer. UNC researchers, led by Kathleen Conway-Dorsey, an assistant professor of cancer epidemiology, analyzed p53 mutations in tumor tissue samples from the patients. UF researchers then identified the FAK protein in the breast cancer samples and performed a statistical analysis, finding that the p53 mutation is associated with overabundance of FAK.
gBasically, tumors of breast cancer patients with p53 had a higher probability of high expression of FAK,h said Golubovskaya. gWe have shown before that FAK overexpression will highly correlate with more aggressive breast cancers.h
Results from the current study could help predict patient prognoses, researchers say. Many patients with mutant p53 and an overabundance of FAK donft fare well, but new therapies could change that by targeting the protein interaction. The next step will involve identifying the types of p53 mutations that contribute to an overabundance in FAK.
The research was supported by Golubovskayafs grant from Komen for the Cure and a National Institutes of Health grant held by surgical oncologist William Cance, chairman of the UF College of Medicinefs Department of Surgery.