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Fig. 4 | Journal of Experimental & Clinical Cancer Research

Fig. 4

From: Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway

Fig. 4

Interactions between PPARγ, WNT pathway and circadian rhythms in cancer. Dysregulation of melatonin and nocturin decreases the expression of PPARγ in cancer. Decreased PPARγ dysregulates Bmal1/Clock heterodimer. Decreased PPARγ expression directly activates the formation of the heterodimer Bmal1/Clock and β-catenin cytosolic accumulation but inhibits the activity of GSK3, the main inhibitor of the WNT/β-catenin pathway. Bmal1/Clock knockout also decreases GSK3 activity and activates the WNT/β-catenin pathway and its downstream gene c-Myc through the activation of the heterodimer Per/Cry. The activation of the WNT/β-catenin pathway by the cytosolic accumulation of the β-catenin and the activation of c-Myc lead to cancer initiation (oxidative stress and chronic inflammation)

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