Regenerating Gene Proteins in Cancer and Inflammation

Regenerating gene (Reg) proteins constitute a family of small, secreted lectin-like factors originally identified in regenerating pancreatic islets. Beyond their role in tissue repair, individual family members have been implicated in both tumourigenesis and inflammatory pathology across a range of organs. In cancer, aberrant expression of Reg proteins can promote cell proliferation, inhibit apoptosis and enhance migration and invasion through activation of key signalling cascades such as PI3K–Akt–mTOR and EGFR–Akt. In parallel, Reg proteins modulate immune responses by influencing macrophage polarisation, dendritic-cell maturation and T-cell priming, thereby shaping an immunosuppressive microenvironment in inflamed or neoplastic tissues. Collectively, these multifunctional molecules serve as biomarkers of disease progression and potential targets for therapeutic intervention in inflammatory disorders and malignancies.

Research from Nature Portfolio

Recent studies have elucidated the transcriptional control of a prominent Reg family member by a gastrointestinal lineage-determining factor. This work demonstrated that the homeobox protein directly binds to the promoter of the Reg gene, coordinating with stemness programmes to drive tumour cell growth under adherent conditions and clonogenic expansion. A microRNA was shown to repress this transcription factor, thereby modulating Reg expression and downstream proliferative signals. These findings link lineage specification, non-coding RNA regulation and Reg-driven tumourigenicity in colorectal cancer models, underscoring potential entry points for intervention.

Regenerating Gene Proteins in Cancer and Inflammation publication trend

The graph below shows the total number of articles in regenerating gene proteins in cancer and inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Regenerating gene (Reg) proteins: Secreted C-type lectin-like factors involved in cell repair, proliferation and differentiation.

PI3K–Akt–mTOR pathway: Intracellular signalling cascade that regulates cell growth, survival and metabolism.

Transcription factor GATA6: DNA-binding protein that directs gene expression programmes in gastrointestinal development and cancer.

MicroRNA: Small non-coding RNA that downregulates target mRNAs post-transcriptionally.

Macrophage M2 polarisation: Alternative activation state of macrophages linked to anti-inflammatory functions and tissue remodelling.

Xenograft model: Transplantation of human cells into immunocompromised mice to study tumour growth in vivo.

JAK/STAT pathway: Cytokine-activated signalling route controlling gene transcription and immune responses.

Epidermal growth factor receptor (EGFR): Cell-surface receptor tyrosine kinase that mediates mitogenic and survival signals.

References

1. Increased expression of REG3A promotes tumorigenic behavior in triple negative breast cancer cells. Breast Cancer Research (2024).
2. Four Decades After the Discovery of Regenerating Islet-Derived (Reg) Proteins: Current Understanding and Challenges. Frontiers in Cell and Developmental Biology (2019).
3. Role of Regenerating Islet-Derived Protein 3A in Gastrointestinal Cancer. Frontiers in Oncology (2019).
4. The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract. International Journal of Molecular Sciences (2021).
5. REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis. Scientific Reports (2015).