A recent study led by UCLA researchers reveals that chronic stress and an unhealthy diet, particularly obesity, may act together to fuel the early development of pancreatic cancer. This groundbreaking research sheds light on how lifestyle factors, such as stress and diet, contribute to one of the deadliest forms of cancer, offering a potential pathway for intervention.
Key Findings
In this preclinical study, the UCLA team identified a crucial molecular mechanism linking stress and obesity to the growth of pancreatic cancer. Specifically, they discovered that both stress-related neurotransmitters and obesity-related hormones activate a protein called CREB, which plays a role in cancer cell growth, through different biological pathways. The study found that stress hormones, such as those produced during social isolation, activate the β-adrenergic receptor/PKA pathway, while obesity-related hormones primarily utilize the PKD pathway. These findings suggest that both stress and obesity promote pancreatic cancer growth by triggering similar biological mechanisms.
Using mouse models, the researchers found that a high-fat diet alone led to the development of precancerous pancreatic lesions. However, when these mice also experienced social isolation-induced stress, the lesions became more advanced, indicating that the combination of obesity and stress exacerbates the development of pancreatic cancer.
Gender Differences in Stress Response
The study also uncovered a notable difference in how stress affected cancer development in male and female mice. Female mice exhibited a stronger response to social isolation stress, which led to more advanced pancreatic lesions compared to their male counterparts. The researchers hypothesize that this difference could be linked to estrogen and the increased activity of the β-adrenergic receptor in females, making them more susceptible to stress-related cancer risks.
Potential for Therapeutic Intervention
These findings highlight the importance of stress hormones and obesity-related signals in promoting cancer growth. The researchers suggest that existing medications, such as beta-blockers—which are commonly used to treat high blood pressure—could be repurposed to help mitigate the effects of stress-related cancer growth. Beta-blockers work by blocking β-adrenergic receptors, which play a significant role in the stress-induced promotion of cancer.
Impact of the Study
The study provides valuable insights into the complex relationship between lifestyle factors, such as chronic stress and obesity, and the development of pancreatic cancer. By understanding how these factors influence cancer growth on a molecular level, the findings open up potential avenues for early intervention, particularly through the repurposing of existing medications. If these insights can be translated into clinical applications, they could offer a promising approach to reducing the risk of pancreatic cancer, particularly for those who are at higher risk due to stress and obesity.
Published Research
The study was published in Molecular Cancer Research, a leading journal in the field of cancer research. The first authors of the study are Xiaoying Sun, a postdoctoral researcher at UCLA, and Yaroslav Teper, a project scientist at the David Geffen School of Medicine at UCLA. The senior authors include Dr. Guido Eibl, a professor at UCLA Health, and Dr. Enrique Rozengurt, a distinguished professor of medicine at UCLA. Other coauthors of the study include James Sinnett-Smith, Mineh Markarian, Dr. Joe Hines, and Dr. Gang Li, all from UCLA Health.
Funding Sources
This research was funded by several prestigious organizations, including the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, the Ronald S. Hirshberg Endowed Chair of Pancreatic Cancer Research, and the Ronald S. Hirshberg Foundation.
Conclusion
The UCLA study underscores the significant impact that lifestyle factors like chronic stress and obesity can have on the early development of pancreatic cancer. By identifying the molecular pathways involved, this research offers new hope for interventions that could reduce cancer risk, particularly through the use of medications like beta-blockers. As the findings continue to evolve, they may provide important insights into how we can prevent or slow the progression of pancreatic cancer, a malignancy that remains one of the most deadly.
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