Mutant KRAS regulates Y chromosome gene in colorectal cancer, driving metastasis and inhibiting immunity

Mutant KRAS regulates Y chromosome gene in colorectalcancer, driving metastasis and inhibiting immunity nature

evaluating hormonal interventions to improve male CRC outcomes have yielded negative or inconclusive results, highlighting a need for a deeper mechanistic understanding of the molecular nuances that drive more aggressive disease in men.First author Jiexi Li, Ph.D.

Cross-species and transcriptomic analyses revealed KDM5D was highly upregulated in these models, and further exploration uncovered its significant involvement in repressing genes governingKDM5D epigenetically disrupts cell junctions, allowing for transition to metastasiscancer cells Additionally, in patient samples, there was a negative correlation between AMOT and KDM5D expression in tumors from males; AMOT expression was lower in KRAS-mutant CRC cell lines from males than from females. Further analysis showed that KDM5D epigenetically represses AMOT, impairing these cell junctions and enabling cancer cells to shift into a metastatic state.

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