Gastric Epithelial Regeneration and Tumorigenesis

The gastric epithelium is a rapidly renewing tissue that maintains a delicate balance between cell proliferation, differentiation and programmed cell death to preserve barrier function and digestive capacity. Resident stem and progenitor cells within distinct glandular zones give rise to specialised lineages including mucus-secreting pit cells, acid-producing parietal cells and enzyme-secreting chief cells. Upon injury or chronic inflammation—most notably driven by Helicobacter pylori infection or chemical insult—homeostatic mechanisms are reprogrammed, leading to metaplastic changes, dysplasia and, ultimately, malignancy. Key signalling pathways such as Wnt/β-catenin, EGFR–ERK, NF-κB and BMP coordinate lineage specification and regenerative proliferation. Genetic alterations (for example in KRAS, TP53 and telomerase genes), epigenetic dysregulation and a permissive microenvironment facilitate tumour initiation and progression. Advances in organoid culture and autochthonous mouse models have provided powerful platforms for dissecting genotype-phenotype relationships and for preclinical testing of targeted interventions aimed at intercepting early tumourigenic events.

Research from Nature Portfolio

Recent studies have established a versatile somatic mouse platform in which defined oncogenic lesions can be introduced directly into the gastric epithelium, faithfully modelling all nonviral molecular subtypes of human gastric carcinoma and revealing genotype-specific patterns of metastasis and immune evasion. This approach has illuminated how distinct driver mutations influence organotropism and therapeutic response. In parallel, single-cell transcriptomic analyses of murine gastric tissue have resolved the dynamic gene-expression programmes guiding progenitor-cell fate decisions, demonstrating that EGFR–ERK signalling unexpectedly promotes pit-cell differentiation while NF-κB activity maintains an undifferentiated progenitor state. Pharmacological modulation of these pathways in vivo has confirmed their dual roles in both homeostatic renewal and early neoplastic transformation.

Gastric Epithelial Regeneration and Tumorigenesis publication trend

The graph below shows the total number of articles in gastric epithelial regeneration and tumorigenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Gastric epithelium: The cell layer lining the stomach, comprising multiple specialised lineages organised in glandular units.

Progenitor cell: A partially differentiated descendant of a stem cell that retains capacity for limited proliferation and lineage commitment.

Organoid: A three-dimensional in vitro culture system that recapitulates key structural and functional features of the native tissue.

Metaplasia: The reversible transformation of one differentiated cell type into another, often in response to chronic injury.

Dysplasia: The presence of abnormal cell morphology and organisation, representing a premalignant stage in epithelial tissues.

Tumourigenesis: The multistep process by which normal cells acquire genetic and epigenetic alterations that culminate in malignant transformation.

References

1. Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease. Nature Cancer (2024).
2. Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis. Nature Communications (2023).
3. H. Pylori‐Facilitated TERT/Wnt/β‐Catenin Triggers Spasmolytic Polypeptide‐Expressing Metaplasia and Oxyntic Atrophy. Advanced Science (2024).
4. The Hyaluronic Acid Receptor CD44 Coordinates Normal and Metaplastic Gastric Epithelial Progenitor Cell Proliferation*. Journal of Biological Chemistry (2013).
5. EGF and BMPs Govern Differentiation and Patterning in Human Gastric Glands. Gastroenterology (2021).