Almost two millennia ago, Galen observed that emotional stress may lead to cancer. However, results of modern-day epidemiological studies that address the connections between stress and cancer remain controversial.
This controversy is largely due to the lack of mechanistic understanding of how stress could influence tumor development and therapy resistance.
While analyzing the anti-apoptotic network in prostate cancer, we have found that epinephrine (at concentrations observed after chronic emotional stress) protects prostate cancer cells from apoptosis via the PKA/BAD mechanism.
Recent experiments show that injections of epinephrine or emotional stress counteract the anti-tumor effects of PI3K inhibitors on prostate cancer xenografts in mice.
Based on these observations, we hypothesize that emotional stress activates anti-apoptotic signaling in prostate cancer cells and, as a result, contributes to the progression of prostate cancer and resistance of advanced prostate cancer to therapies.
If this hypothesis is confirmed, it will provide a mechanistic explanation for the connection between emotional stress and cancer.
The project will be developed in the following directions:
- prostate cancer xenografts and a transgenic mouse model of prostate cancer will be used to test the role of emotional stress and depression in cancer development and therapeutic sensitivity
- the signaling pathways activated by stress hormones and their role in apoptosis regulation will be analyzed
- stress hormone levels in prostate cancer patients and their responses to therapies will be assessed