Cytochrome P450 enzymes as modulators of oncogenic signaling via the Wnt/β-catenin signaling pathway

TL;DR

This paper reviews how cytochrome P450 enzymes might influence cancer development by modulating the Wnt/β-catenin signaling pathway.

Contribution

The paper highlights a previously undervalued role of CYP enzymes in regulating the Wnt/β-catenin signaling pathway, suggesting new mechanisms in cancer development.

Findings

CYP enzymes may affect β-catenin pathway activity beyond their traditional roles in detoxification.

The Wnt/β-catenin pathway is a newly recognized regulator of CYP enzyme expression.

There is evidence suggesting a bidirectional regulatory relationship between CYP enzymes and oncogenic signaling.

Abstract

Enzymes from the cytochrome P450 (CYP) superfamily, especially from families CYP1, CYP2, and CYP3, play a decisive role in phase I of drug and xenobiotic metabolism in mammalian organisms. The enzymes are responsible for metabolic conversion and detoxification of a plethora of foreign molecules. Metabolic conversion of pro-carcinogenic compounds links CYP enzyme activities to cancer development, while in addition oncogenic pathways have been shown to regulate the expression of CYP genes, together with the well-known regulation by nuclear receptors acting as ligand-activated transcription factors triggered by exposure to xenobiotics. Specifically, the Wnt/β-catenin signaling pathway is among the recently established transcriptional regulators of CYP enzymes. β-Catenin is well-known as a key player in organism development and, when aberrantly activated, a major oncogenic driver of carcinogenesis. While the latter phenomena are rather well-described, new evidence suggests that CYP enzymes themselves may, under certain conditions, also affect the activity of the β-catenin pathway and thereby could impact on carcinogenesis in a way different from toxifying or detoxifying foreign compounds. This review focuses on the currently available knowledge about the regulation of β-catenin-dependent signaling by CYP enzymes. The synopsis of data reveals the possibility of a previously undervalued role of CYPs in the regulation of Wnt/β-catenin signaling, and possible molecular mechanisms are highlighted.

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