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

**Authors:** Albert Braeuning

PMC · DOI: 10.1007/s00204-025-04295-7 · 2026-01-17

## 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.

## Key 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.

## Linked entities

- **Genes:** PPIG (peptidylprolyl isomerase G) [NCBI Gene 9360], CYP1A1 (cytochrome P450 family 1 subfamily A member 1) [NCBI Gene 1543], CYP2 (cyclophilin 2) [NCBI Gene 4961207], PPIF (peptidylprolyl isomerase F) [NCBI Gene 10105], ctnnb1.S (catenin beta 1 S homeolog) [NCBI Gene 380441]
- **Proteins:** ctnnb1.S (catenin beta 1 S homeolog)

## Full-text entities

- **Genes:** PPIF (peptidylprolyl isomerase F) [NCBI Gene 10105] {aka CYP3, CyP-M, Cyp-D, CypD}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CYP1A1 (cytochrome P450 family 1 subfamily A member 1) [NCBI Gene 1543] {aka AHH, CP11, CYP1, CYPIA1, P1-450, P450-C}
- **Diseases:** cancer (MESH:D009369), carcinogenic (MESH:D011230), carcinogenesis (MESH:D063646), oncogenic (MESH:D000074723)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13043527/full.md

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Source: https://tomesphere.com/paper/PMC13043527