The study discovered connections between the PI3K/Akt and p53 pathways that provide potential targets for novel cancer treatments.
Cells manufacture a protein called p53, which functions within the cell nucleus to react to stress, but mutations in the gene that makes p53 are the most common genetic abnormalities in cancer. Runaway cell proliferation in cancer is also often linked to mutations that activate a cell’s surface-located pathway called PI3K/Akt.
A team led by UW–Madison cancer researchers Richard A. Anderson and Vincent Cryns has discovered a direct link between the p53 and PI3K/Akt pathways. The findings, recently published in the journalidentified links in the pathways that make promising targets for new cancer treatments. Instead of entering apoptosis — the proactive process of cell suicide which removes damaged cells — the cancer cells repaired their chemotherapy-damaged DNA and went on growing and dividing, promoting cancer growth.“Our finding that the PI3K/Akt pathway is anchored on p53 in the nucleus was entirely unexpected,” says Cryns, a physician-scientist and professor at UW School of Medicine and Public Health.“These results also have critical implications for cancer treatment,” Cryns says.
The team had previously shown that PIPKIa stabilizes the p53 protein, allowing it to be active. When PIPKIa was turned off, p53 levels inside the cell fell sharply. In the new study, the team showed that blocking PIPKIa by genetic approaches or a drug triggered cancer cell death by preventing p53 from activating Akt in the cell nucleus.