PLX294746

GSE106330: Degree of Tissue Differentiation Dictates Susceptibility to BRAF-driven Colorectal Cancer

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

In murine models, we find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation and senescence. This corresponds to inefficient tumor formation in oncogenic BRAF mouse models of colon cancer. By reducing levels of differentiation in the gut 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 mutant BRAF 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. SOURCE: Michael VerziVerzi Rutgers, the State University of New Jersey