Estrogen Signaling and Colorectal Cancer Dynamics

The dynamic interplay between oestrogen signalling and colorectal carcinogenesis has emerged as a critical area in understanding sex-based differences in incidence and progression. Oestrogens mediate their effects through two principal nuclear receptors, ERα and ERβ, which exert distinct—and at times opposing—actions within colonic epithelium. ERβ predominates in healthy colon tissue and is associated with anti-proliferative, pro-apoptotic and anti-inflammatory responses that collectively suppress tumour initiation and progression. Loss of ERβ expression accompanies tumour development, suggesting its protective role is compromised during malignant transformation. Conversely, aberrant ERα upregulation in colorectal tumours has been correlated with enhanced Wnt/β-catenin signalling, weakened cell–cell junction integrity and increased metastatic potential. Beyond the epithelium, oestrogen signalling shapes the tumour microenvironment by modulating immune cell recruitment, cytokine profiles and stromal interactions, with implications for immunotherapy responsiveness. The balance of oestrogenic effects is further influenced by circulating hormones, receptor polymorphisms and exogenous modulators such as phytoestrogens. Together, these insights offer a nuanced framework linking molecular pathways to clinical outcomes and point to the potential of receptor-targeted strategies—ranging from selective agonists and antagonists to combination approaches with immunomodulatory agents—to refine prevention and treatment of colorectal cancer, bridging mechanistic understanding with pragmatic interventions.

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Estrogen Signaling and Colorectal Cancer Dynamics publication trend

The graph below shows the total number of articles in estrogen signaling and colorectal cancer dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Oestrogen receptor alpha (ERα): A nuclear receptor that binds oestrogens and regulates gene expression, often associated with proliferative and pro-metastatic effects in colorectal cancer.

Oestrogen receptor beta (ERβ): A nuclear receptor subtype that mediates anti-proliferative, pro-apoptotic and anti-inflammatory responses in colonic epithelium, acting as a tumour suppressor.

Tumour microenvironment: The complex milieu surrounding a tumour, comprising immune cells, stromal elements and signalling molecules that influence cancer growth and response to therapy.

Wnt/β-catenin signalling: A conserved pathway that controls cell proliferation and differentiation; its dysregulation contributes to colorectal tumour initiation and progression.

References

1. Intestinal estrogen receptor beta modulates the murine colon tumor immune microenvironment. Cancer Letters (2025).
2. High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer. Cell Communication and Signaling (2024).
3. Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies. Biology of Sex Differences (2024).
4. Mechanisms of Action of Phytoestrogens and Their Role in Familial Adenomatous Polyposis. Pharmaceutics (2024).
5. Estrogen Receptor-β Gene Cytosine-Adenine (ESR2-CA) Repeat Polymorphism in Postmenopausal Colon Cancer. International Journal of Molecular Sciences (2023).