Sox9 protein enables molecular 'time travel' that can lead to colorectalcancer danafarber ScienceAdvances
Using mouse models and tumor models called patient-derived organoids, they found that the cells undergo a type of molecular time travel that reverts them back to an embryonic state. Fetal genes that are silenced in adults are inappropriately turned on, endowing greater cellular flexibility. But instead of creating functional cells that migrate to the surface, they create immature, non-functional cells that clump together to form benign growths called adenomas.
Over 80% of colorectal cancers show signs of mutations that are related to this immature state of impaired differentiation. The researchers also found that this molecular time travel depends on a protein called Sox9 and that blocking Sox9 in mouse models prevented adenoma formation, enabled cells to mature, and resulted in the death of pre-cancer cells. The work builds on previous research from the Sethi Lab at Dana-Farber suggesting that human colon cancer depends on Sox9.
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