Thursday, July 6, 2017, Cleveland: Poor diet is associated with 80% of colorectal cancer cases, but the exact pathways by which diet leads to cancer are not known.
In a newly published study, Cleveland Clinic researchers have identified a specific molecular pathway that plays a key role in the link between a high-fat diet and tumor growth in the colon.
In the July 6 issue of Stem Cell Reports, the team showed in pre-clinical models that cancer stem cell growth in the colon was enhanced by a high-fat, Western diet. Cancer stem cells are a subset of resilient, aggressive malignant cells that are believed to be partially responsible for spread and recurrence of cancer.
Furthermore, when the researchers blocked the JAK2-STAT3 cellular signaling pathway, a widely studied pathway known to promote tumor growth, the spike in cancer stem cell growth caused by the high-fat diet declined.
This study provides more insight into how the JAK2-STAT3 pathway is linked to diet-related cancer. Pinpointing the exact mechanism can help researchers develop therapeutics to counteract the negative effects of a Western diet on colorectal cancer.
Colorectal cancer is the third most common cancer in the United States with more than 130,000 cases reported annually. The disease arises as a result of a combination of several genetic, epigenetic and environmental causes, such as diet.
"We have known the influence of diet on colorectal cancer. However, these new findings are the first to show the connection between high-fat intake and colon cancer via a specific molecular pathway," said Matthew Kalady, M.D., co-author of the study, colorectal surgeon, and Co-Director of the Cleveland Clinic Comprehensive Colorectal Cancer Program. "We can now build upon this knowledge to develop new treatments aimed at blocking this pathway and reducing the negative impact of a high-fat diet on colon cancer risk."
The team analyzed human colorectal cancer-free survival data in the Cancer Genome Atlas and evaluated primary and metastasized colorectal cancer specimens via microarray analysis. They further verified the link between high-fat diet and stem cell maintenance in obesity-resistant mice.
"These findings also provide a new way in which cancer stem cells are regulated and provide insight into how environmental influences, such as diet, can alter cancer stem cell populations in advanced cancers," said Justin D. Lathia, Ph.D., Associate Professor in the Department of Cellular and Molecular Medicine, Lerner Research Institute, and co-author of the study.
Senior author of the study was the late Noa Noy, Ph.D., and first author was Sheelarani Karunanithi, Ph.D. The laboratories of Drs. Ofer Reizes, Ph.D., Justin D. Lathia, Ph.D., and Matthew Kalady, M.D., participated in the study. This work was supported by NIH grant R01DK088969.
After the embargo lifts, the study will be available at: http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(17)30265-5
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Among Cleveland Clinic's 51,000 employees are more than 3,500 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic's health system includes a 165-acre main campus near downtown Cleveland, 10 regional hospitals, more than 150 northern Ohio outpatient locations — including 18 full-service family health centers and three health and wellness centers — and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2016, there were 7.1 million outpatient visits, 161,674 hospital admissions and 207,610 surgical cases throughout Cleveland Clinic's health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.
About the Lerner Research Institute
The Lerner Research Institute is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. Lerner researchers publish ~1,500 articles in peer-reviewed biomedical journals each year. Lerner's total annual research expenditure was $260 million in 2016 (with $140 million in competitive federal funding, placing Lerner in the top five research institutes in the nation in federal grant funding). Approximately 1,500 people (including approximately 200 principal investigators, 240 research fellows, and about 150 graduate students) in 12 departments work in research programs focusing on heart and vascular, cancer, brain, eye, metabolic, musculoskeletal, inflammatory and fibrotic diseases. The Lerner has more than 700,000 square feet of lab, office and scientific core services space. Lerner faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University – training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The Lerner is a significant source of commercial property, generating 64 invention disclosures, 15 licenses, 121 patents, and one new spinoff company in 2016. Visit us at http://www.lerner.ccf.org. Follow us on Twitter at http://www.twitter.com/CCLRI.