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LGR5 Expression Predicting Poor Prognosis Is Negatively Correlated with WNT5A in Colon Cancer.

Lubna M Mehdawi1, Souvik Ghatak1, Payel Chakraborty1

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WNT5A signaling, including the peptide Foxy5, suppresses colon cancer growth by reducing LGR5/RSPO3 and β-catenin activity. This inhibits cancer stemness and VEGFA, offering new therapeutic avenues.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • WNT/β-catenin signaling is crucial for colon cancer progression.
  • WNT5A and Foxy5 are known to inhibit β-catenin signaling through unclear mechanisms.

Purpose of the Study:

  • Investigate WNT5A's impact on LGR5, RSPO3, β-catenin activity, and VEGFA in colon cancer.
  • Determine the relationship between WNT5A and colon cancer stemness markers like DCLK1.

Main Methods:

  • Analysis of colon cancer patient cohorts (immunohistochemistry, qRT-PCR).
  • In vitro and in vivo experiments using colon cancer cell lines (Western blotting, RT-PCR, assays, immunofluorescence).

Main Results:

  • WNT5A expression negatively correlated with LGR5/RSPO3 and DCLK1 in patient cohorts.
  • WNT5A signaling suppressed β-catenin activity, LGR5, RSPO3, VEGFA, and cancer stemness markers.
  • Foxy5 peptide mimicked WNT5A's inhibitory effects.

Conclusions:

  • WNT5A and Foxy5 reduce LGR5/RSPO3 expression and β-catenin activity.
  • This inhibition impacts colon cancer stemness and VEGFA expression.
  • WNT5A/Foxy5 represent potential therapeutic strategies for colon cancer.