Study Reveals How Dietary Fat May Help Colorectal Cancer Spread

THE BRONX, N.Y., Sept. 24, 2026 /PRNewswire/ -- Metastasis—the spread of cancer from a primary tumor to other parts of the body—causes most cancer-related deaths. But how primary tumor cells gain this deadly ability to spread remains largely unknown. Now, research led by a scientist at Montefiore Einstein Comprehensive Cancer Center (MECCC) has identified a mechanism that enables colorectal cancer cells to spread to other organs and found that high-fat diets can activate this mechanism. The study, conducted primarily in mice, was published today online in Science.

"Cancer stem cells are a small group of cells within a tumor that can renew themselves, produce other cancer cells, and shift from one cellular state to another," said Swagata Goswami, Ph.D., lead author of the study and assistant professor of molecular pharmacology at Albert Einstein College of Medicine. "We found that some colorectal cancer stem cells activate a program normally used to repair the intestinal lining. In cancer cells, however, this regenerative program enhances their ability to form tumors elsewhere in the body."

Dr. Goswami and her colleagues found that this shift is driven by YAP, a protein that regulates cell growth and tissue repair. The researchers believe that this regenerative state may help cancer stem cells adapt to the challenges of breaking away from the primary tumor and establishing themselves in a distant organ.

High-Fat Diets and Cancer Spread
The researchers also discovered a connection between dietary fat and this change in cancer stem cells. In several mouse models of colorectal cancer, a high-fat diet increased the production of ceramides, a type of fat molecule found naturally in cells. The higher ceramide levels activated YAP and increased the number of cancer stem cells associated with metastasis.

Additional experiments provided further evidence that ceramides were helping to drive this process. When the researchers genetically blocked the process that produces ceramides, YAP activity and the regenerative state decreased, as did liver metastases, while primary tumor mass was unaffected. Conversely, preventing cancer cells from breaking down ceramides increased YAP activity and metastasis.

"Obesity is a recognized risk factor for developing colorectal cancer," Dr. Goswami noted. "Our findings in mouse models suggest that excess fat intake, by spurring ceramide production, may also promote the spread of colorectal tumors. More research is needed to determine whether the same process can be safely targeted in patients."

Comparing Different Cancer Stem Cells
The researchers next tested whether cancer stem cells in the regenerative state were especially capable of initiating metastases. They separated tumor cells in the regenerative state (tumor cells with high expression of regenerative markers) from other cancer cells in primary tumors and transplanted the two groups into mice. The regenerative cells did not produce larger primary tumors, but they did produce substantially more liver meastases. When the researchers removed regenerative cancer stem cells from established tumors, metastases to the liver—the organ most often targeted when colorectal cancer spreads—were greatly reduced without reducing the size of the primary tumors.

"These findings suggest that the ability to form metastases reflects a change in the state of some cancer stem cells rather than simply faster or more aggressive growth of the original tumor," said Dr. Goswami. "Selectively targeting regenerative cancer stem cells within primary tumors might prevent those tumors from spreading."

The researchers also found that among patients whose cancer had spread to the liver, genes associated with the regenerative state were more active in tumors from patients with obesity than in those from leaner patients.

"Many people with colorectal cancer are diagnosed and treated before metastasis is detected, yet a substantial proportion later relapse with metastatic disease," said Dr. Goswami. "Our findings identify several possible approaches to preventing or limiting metastasis, including blocking ceramide production, inhibiting YAP, and eliminating regenerative cancer cells from primary tumors. Such approaches could complement treatments aimed at removing the primary tumor."

The research began during Dr. Goswami's postdoctoral training in the laboratory of co-author Ömer H. Yilmaz at the Massachusetts Institute of Technology. An additional Einstein author was Chesta Jain. Other authors were Qiming Zhang, Abdullah Burak Yildiz, Upasana Das Adhikari, Akhouri Kishore Raghawan, Manon Bulliard, Sabhyata Sedhain, Odai Darawshi, Cigdem Elif Celik, Feyza Cansiz, Constantin P. Krempe, Jonas Rösler, Gabriele Allies, Sven W. Meckelmann, Chiashin Chi, Felix-Levin Hormann, Sven Heiles, Joseph Sedlak, Wesley Grace, George Eng, Ethan Reich, Chiara Alquati, Kevin J. Williams, Benjamin J. Read, Edrees H. Rashan, Zhixin Li, Anup Jnawali, Jose A. Ortiz, Charles A. Whittaker, Osman H. Yilmaz, Vikram Deshpande, Oliver J. Schmitz, Albert Sickmann, Autumn G. York, Douglas S. Kwon, Ulf Neumann, Maria Fedorova, Matthew G. Vander Heiden, Besim Ogretmen, Nilay S. Sethi, and Alpaslan Tasdogan.

The paper, "Ceramide synthesis mediates colorectal cancer metastasis through a YAP-driven regenerative program," was supported by National Institutes of Health grants R00CA287057, K99CA287057 and K00CA245813, R01CA211184, R01CA034992, U54CA224068, R01CA285926, R0CA203628, DE016572, P30CA014051, R35CA242379, C06RR015455, P30CA138313, P30GM103339, K08CA277011 and R01CA292507; Cancer Research Institute grant CRI4478; Department of Defense award CA201084; German Research Foundation Emmy Noether Award DFG467788900; European Research Council Starting Grant 101078355; and additional support from the MIT Stem Cell Initiative, MIT Center for Precision Cancer Medicine, Ludwig Center at MIT, Ministry of Culture and Science of the State of North Rhine-Westphalia, NRW-Nachwuchsgruppenprogramm, Berlin Senate Department for Science, Health and Care, German Federal Ministry of Research, Technology and Space, SC SmartState Endowment in Lipidomics, Stiftung Experimentelle Biomedizin, Jimmy Fund Walk's Opiela Family, Craig Baskin, Dave and Carol Fischer, and Howard and Wendy Cox.

About Montefiore Einstein Comprehensive Cancer Center
Montefiore Einstein Comprehensive Cancer Center (MECCC) is a National Cancer Institute (NCI)-designated comprehensive cancer center and a national leader in cancer research and clinical care located in the racially and ethnically diverse borough of the Bronx, N.Y. MECCC combines the exceptional science of Albert Einstein College of Medicine with the multidisciplinary and team-based approach to cancer clinical care at Montefiore Health System. Founded in 1971 and an NCI-designated cancer center since 1972, MECCC is redefining excellence in cancer research, clinical care, education and training, and community outreach and engagement. Its mission is to reduce the burden of cancer for all, especially people from historically underrepresented groups.

About Albert Einstein College of Medicine
Albert Einstein College of Medicine is one of the nation's premier academic centers for basic science research, clinical investigation, and biomedical education. Located in the Bronx, Einstein is home to nearly 1,000 M.D., Ph.D., and M.D./Ph.D. students and more than 2,000 full-time faculty members. Einstein receives approximately $200M in funding from the National Institutes of Health (NIH) each year and houses six NIH-funded research centers, in cancer, intellectual and developmental disabilities, clinical and translational research, AIDS, and two in diabetes. In partnership with Montefiore Health System, Einstein advances clinical and translational research to accelerate the pace at which new discoveries become the treatments that benefit patients. For more information, please visit einsteinmed.edu, and follow us on Instagram, LinkedIn, Twitter, Facebook, and view us on YouTube.

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