A new study led by UCLA researchers reveals that chronic stress, combined with an unhealthy diet, may play a significant role in the early development of pancreatic cancer, highlighting the impact of lifestyle factors on this aggressive and often fatal cancer. The study, published in Molecular Cancer Research, uncovers a crucial molecular mechanism through which stress and obesity may trigger cancer cell changes in the pancreas.
Using preclinical models, the researchers discovered that both stress and obesity activate specific proteins linked to the growth of cancer cells. Stress hormones and obesity-related hormones stimulate a protein called CREB, which is associated with cancer cell proliferation. The pathways differ, with stress hormones primarily activating the β-adrenergic receptor/PKA pathway, while obesity-related signals engage the PKD pathway. This suggests that both factors contribute to pancreatic cancer growth through similar molecular mechanisms.
In experiments with mice, a high-fat diet alone led to the development of precancerous pancreatic lesions. However, when combined with social isolation stress, the lesions progressed further, indicating that stress could exacerbate the effects of an unhealthy diet on cancer development.
The study also revealed a gender difference in the impact of social isolation stress, with female mice showing a stronger susceptibility to cancer development compared to male mice. Researchers speculate that estrogen and increased β-adrenergic receptor activity in females may make them more vulnerable to stress-related cancer risks.
The findings underscore the role of stress and obesity hormones in triggering cancer-promoting pathways that may accelerate the onset of pancreatic cancer. As a potential solution, the researchers suggest exploring the repurposing of existing medications, such as beta-blockers, to reduce this risk. Beta-blockers, commonly used to treat high blood pressure, could potentially block the cancer-promoting effects of stress-related hormones.
The study was led by Xiaoying Sun, a postdoctoral researcher at UCLA’s Departments of Medicine and Surgery, and Yaroslav Teper, a project scientist at the David Geffen School of Medicine. The senior authors include Dr. Guido Eibl, a professor of surgery at UCLA Health, and Dr. Enrique Rozengurt, a distinguished professor of medicine and chief of research at UCLA’s Division of Digestive Diseases. The team also includes researchers from UCLA’s Jonsson Comprehensive Cancer Center: James Sinnett-Smith, Mineh Markarian, Dr. Joe Hines, and Dr. Gang Li.
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