Researchers at the Stevens Institute of Technology have published a study in Cell Death & Disease examining the origins of colorectal cancer.
Key Findings
The research identifies two distinct pathways through which tumors can form in the intestinal epithelium, potentially offering insight into treatment resistance.
Led by Assistant Professor Ansu Perekatt, the study concentrated on Lgr5-positive stem cells, which are responsible for renewing the intestinal lining.
"Tumors can originate not only from damaged stem cells, but also from mature cells that revert to a stem-like state."
Researchers identified two mechanisms for tumor development:
- "Bottom-up" pathway: Tumors originate from mutations in normal stem cells.
- "Top-down" pathway: Mature intestinal cells undergo dedifferentiation, reverting to a stem-like state and acquiring de-novo stemness before becoming cancerous.
In mouse models, mutant stem cells were eventually replaced by healthy cells. However, a subset of progenitor cells that underwent dedifferentiation became cancerous and formed tumors. These tumors exhibited enhanced survival mechanisms, including protection against oxidative stress.
Context and Implications
Colorectal cancer is the second leading cause of cancer death in the United States. Incidence rates are rising among adults under 55. Risk factors cited in broader research include Western dietary patterns, sedentary lifestyles, obesity, and altered gut microbiomes.
This dual origin may explain why some tumors resist treatment: Therapies targeting only cancer cells derived from stem cells may not prevent relapse if dedifferentiated cells are not also addressed.
"Comprehending the process of reversion to stemness could inform the development of more effective therapeutic strategies for colorectal cancer."
— Assistant Professor Ansu Perekatt