Related Experiment Video
Updated: Feb 16, 2026

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer
Kevin Tong1, Oscar Pellón-Cárdenas1, Veerin R Sirihorachai2
1Department of Genetics, Rutgers University, Human Genetics Institute of New Jersey (HGINJ), 145 Bevier Road, Piscataway Township, NJ 08854, USA; Rutgers Cancer Institute of New Jersey (CINJ), 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Abstract:
Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2), stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.
Related Concept Videos
One-Degree-of-Freedom System
A one-degree-of-freedom system is defined by an independent variable that determines its state and behavior. One example of a one-degree-of-freedom system is a simple harmonic oscillator, such as a...
Degrees of Freedom
For example, suppose there are three unknown numbers whose mean is 10; although we can freely assign values to the first and second numbers, the value of the last number can not be arbitrarily assigned.
Degrees of Freedom
For example, suppose there are three unknown numbers whose mean is 10; although we can freely assign values to the first and second numbers, the value of the last number can not be arbitrarily...
Degree of Unsaturation
The degree of unsaturation for hydrocarbons is U = (2C + 2 − H) / 2, where C is the number of carbon atoms and H is the number of hydrogen atoms.
Radian and Degree Measure
Magnetic Susceptibility and Permeability
When diamagnetic materials are placed under an external magnetic field, the moments opposite to the field are induced. Hence, the susceptibility for diamagnets has a minimal negative value of 10-5–10-6. Since...

