Abstract
14–3-3ζ is becoming an important marker and possible treatment target because many studies link it with cancer recurrence and resistance to chemotherapy. When cancer cells make too much 14–3-3ζ, they tend to survive better, especially under stressful conditions, and they can grow even without attachment, which is usually a sign of more aggressive behavior. On the other hand, when the level of 14–3-3ζ is lowered, tumors grow slower and the cells become more sensitive to different anticancer drugs. In clinical settings high 14–3-3ζ can work as prognostic biomarker, helping to identify patients whose tumors might not respond fit to standard treatments, allowing doctors to think about more personalized therapy options. This protein also interacts with several cancer-related pathways for example working together with HER2, which can push tumors to become more invasive, and harder to treat. Many cancers show amplification of the 14–3-3ζ gene and this usually correlates with worse outcomes for patients. Even though scientists are still figuring out how directly target 14–3-3ζ, a lot of studies suggest that stopping this protein or blocking the signals it activates might make cancer cells respond better in chemo and slow the tumor from getting worse [14]. So overall, going after 14–3-3ζ looks like the pretty promising approach for dealing with therapy resistance, and it could maybe help improve patient outcomes in the future. GRAPHICAL ABSTRACT: The 14-3-3 protein family can actually act in two totally opposite ways in cancer, which makes it kinda tricky to study. In some situations, 14-3-3 works like an anti-cancer helper because it stabilizes the p53 protein. When p53 is stable, it can stop the cell cycle and even push damaged cells into apoptosis, so those cells don’t keep dividing. But in other cases, 14-3-3 ends up doing the complete opposite and helps the tumor grow. It mainly does this by turning on the PI3K/AKT pathway, which then causes NF-κB to move into the nucleus. Once NF-κB is in the nucleus, it switches on a bunch of genes that let cancer cells survive longer, divide faster, and even migrate or invade other tissues. So overall, 14-3-3 proteins can either slow cancer down or help it get worse, depending on which signaling pathway is taking over in the cell. [Image: see text]