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Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5-CD44+ cells

ABSTRACT: Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5-CD44+ cells

PROVIDER: PRJNA533540 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8926560.fastq.gz	Fastqsanger.gz
	SRR8926561.fastq.gz	Fastqsanger.gz
	SRR8926554.fastq.gz	Fastqsanger.gz
	SRR8926555.fastq.gz	Fastqsanger.gz
	SRR8926556.fastq.gz	Fastqsanger.gz

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Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5-CD44+ cells

Project description:We report the gene expression profiles of gastric squamous-columnar junction cancer derived from the mice with conditionally inactivation of Trp53 and Rb1 genes in Lgr5+ cells

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Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5<sup>-</sup>CD44<sup>+</sup> cells.

Project description:Areas of a junction between two types of epithelia are known to be cancer-prone in many organ systems. However, mechanisms for preferential malignant transformation at the junction areas remain insufficiently elucidated. Here we report that inactivation of tumor suppressor genes Trp53 and Rb1 in the gastric squamous-columnar junction (SCJ) epithelium results in preferential formation of metastatic poorly differentiated neoplasms, which are similar to human gastroesophageal carcinoma. Unlike transformation-resistant antral cells, SCJ cells contain a highly proliferative pool of immature Lgr5-CD44+ cells, which are prone to transformation in organoid assays, comprise early dysplastic lesions, and constitute up to 30% of all neoplastic cells. CD44 ligand osteopontin (OPN) is preferentially expressed in and promotes organoid formation ability and transformation of the SCJ glandular epithelium. OPN and CD44 overexpression correlate with the worst prognosis of human gastroesophageal carcinoma. Thus, detection and selective targeting of the active OPN-CD44 pathway may have direct clinical relevance.

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Epithelial expressions of Gata4 and Sox2 regulate murine specification of the squamous–columnar junction via MAPK/ERK signaling

Project description:The squamous–columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal–distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells at the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.

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