IHV Researchers Publish Study in Oncogene Uncovering New Insights into Colorectal Cancer Metastasis

Researchers from the Institute of Human Virology (IHV), in collaboration with colleagues from the University of Maryland School of Medicine (UMSOM), have published new findings in the high-impact journal Oncogene that advance our understanding of how colorectal cancer spreads and identify a promising therapeutic target for preventing metastasis.

The study, "HIF-1α integrates lipogenic FASN and glycolytic GLUT3 to overcome intratumor oxidative and hypoxic stress for colorectal cancer metastasis," was led by Yan Liu, PhD, Assistant Professor, and brought together investigators from the IHV Division of Immunotherapy, the Department of Surgery and the Marlene and Stewart Greenebaum Comprehensive Cancer Center, and the Division of Gastroenterology & Hepatology within the UMSOM Department of Medicine.

Colorectal cancer remains one of the leading causes of cancer-related deaths worldwide, with metastatic disease accounting for most of the patient mortality. As tumors grow, they encounter challenging conditions such as low oxygen levels and oxidative stress. To survive and spread, cancer cells must adapt to these hostile environments.

In this study, the research team identified HIF-1α as a central regulator that enables colorectal cancer cells to withstand these stresses by coordinating two key metabolic pathways through FASN and GLUT3. Together, these pathways allow cancer cells to maintain energy production, resist cellular stress, and increase their ability to invade other tissues and metastasize.

Using laboratory and preclinical models, the investigators demonstrated that blocking HIF-1α activity significantly reduced tumor growth and prevented the spread of colorectal cancer to the lungs. The study also showed that delivering the HIF-1α inhibitor echinomycin using lipid nanoparticles effectively disrupted the stress-response mechanisms that cancer cells rely on to survive, highlighting a promising therapeutic strategy for metastatic colorectal cancer.

The findings provide new insight into the metabolic adaptations that fuel cancer progression and suggest that targeting the HIF-1α–FASN/GLUT3 pathway could offer a new approach for treating advanced colorectal cancer.

"This work helps us better understand how colorectal cancer cells adapt to survive under stressful conditions within tumors. By identifying the mechanisms that drive metastasis, we can begin developing therapies that interrupt these processes before the disease spreads," Said Dr. Liu. “The study shows that HIF-1α helps colorectal cancer cells coordinate metabolic and stress-adaptive programs through FASN, GLUT3, and NRF2, supporting tumor growth and lung metastasis. It also shows that LNP-formulated echinomycin can suppress these HIF-1α-driven programs and reduce tumor growth and metastatic burden in preclinical models.”

The publication represents another example of IHV's commitment to advancing innovative biomedical research through multidisciplinary collaboration and translating scientific discoveries into future therapeutic strategies.

Read the full publication here: HIF-1α integrates lipogenic FASN and glycolytic GLUT3 to overcome intratumor oxidative and hypoxic stress for colorectal cancer metastasis (Oncogene).