Fig. 8: Suppression of the interaction between β-catenin and PAF1C by CDX1 and CDX2. | Cell Death & Disease

Fig. 8: Suppression of the interaction between β-catenin and PAF1C by CDX1 and CDX2.

From: CDX1 and CDX2 suppress colon cancer stemness by inhibiting β-catenin-facilitated formation of Pol II–DSIF–PAF1C complex

Fig. 8

A IP assays showing the effects of wt-Cdx1/2 and their homeodomain (HD) mutants on the interaction of β-catenin-S33Y (β-Cat.) with SPT5, PAF1 components, and RPBs. The indicated proteins were expressed in the IP assays along with FLAG-β-catenin-S33Y. B IP assays showing the effects of wt-Cdx1/2 and their HD mutants on the interaction of FLAG-TCF4 with PA-β-catenin-S33Y (β-Cat.), Myc-tagged SPT5, PAF1 components, and RPBs. In the IP assays, the indicated proteins were expressed along with FLAG-TCF4. C ChIP-qPCR data showing the relative occupancy (mean ± SD) of β-catenin at the indicated positions in LGR5 after expressing wt-Cdx2 or Cdx2-RN:2A for 1 day in DLD1-TetOff cells, when compared with that in cells with Cdx unexpressed. P-values were calculated using a Student′s t-test. D Transcriptional mechanism underlying the inhibition of stable β-catenin by CDX1/2 via DSIF and PAF1C complexes, resulting in the suppression of colon cancer stemness. First, TCF4 recruits β-catenin to its target gene. β-Catenin then recruits DSIF and PAF1 complexes to the Pol II complex to facilitate the formation of the active Pol II complex, which promotes colon cancer stemness. CDX1/2 suppress these processes. DSIF and PAF1 complexes act as platforms that integrate and funnel oncogenic and tumor-suppressive signals into gene expression, thereby controlling cancer stemness.

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