New molecular insights reveal potential colon cancer targets

Aug '25 (edited) • 💡Research & Education

Researchers have uncovered a key mechanism by which cancer stemness in colon cancer could be targeted therapeutically.

A study led by Professor Koji Aoki (University of Fukui, Japan) and published in Cell Death & Disease revealed that CDX1 and CDX2 transcription factors suppress cancer cell stemness by blocking β-catenin from activating stemness genes like LGR5 and CD44.

Key Findings:

Loss of CDX1 or CDX1/2 in mice led to more aggressive, invasive tumours with elevated LGR5 and CD44 expression.
Reintroduction of CDX1/2 into cancer cells reduced stemness gene expression, confirming their tumour-suppressive role.
CDX1/2 bind to a site downstream of the LGR5 gene, overlapping with β-catenin’s binding site.
Although CDX1/2 created a more open chromatin structure (often linked to gene activation), they reduced recruitment of Pol II transcriptional machinery, including DSIF and PAF1 complexes.
CDX1/2 directly interfered with β-catenin’s ability to assemble active transcription complexes via their homeodomains.

Therapeutic Implications:

DSIF and PAF1 have been identified as critical regulators of colon cancer stemness.
These complexes act as “transcriptional platforms,” integrating both tumour-suppressive and oncogenic signals.
Targeting DSIF and PAF1 could open new therapeutic strategies for colon cancer.

Professor Aoki emphasized that deeper investigation into these transcriptional mechanisms could pave the way for drugs designed to effectively block cancer stemness in colon cancer.

https://www.ddw-online.com/new-molecular-insights-reveal-potential-colon-cancer-targets-35793-202507/

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