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Claudin-6 increases SNAI1, NANOG and SOX2 gene expression in human gastric adenocarcinoma AGS cells

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Abstract

Background

Gastric cancer is a heterogeneous disease associated to deregulated gastric epithelia tight junction barrier function and di novo expression of claudin-6; these changes are associated with epithelial-mesenchymal transition, enhanced invasiveness, metastatic progression, resistance to chemotherapy, and poor prognosis. Gastric cancer stem cells represent a rare population of cells within the tumor implicated in tumor growth and higher tumorigenic capacity. The possible relation between claudin-6 expression and the expression of some markers associated to epithelial mesenchymal transition and cancer stem cells in gastric cancer cells have never been explored.

Methods and results

CD44, CD24, Twist, Villin, DCLK1, claudin-6, NANOG, E-Cadherin, SOX2, and SNAI1 expression was evaluated by immunofluorescence and cytofluorometry in wild type and Claudin-6 transfected AGS cells. Cell migration assays were also performed. Differentially expressed genes and biological processes analysis was performed to determine gene preponderance. The results showed that claudin-6 overexpression enriched the CD44 + /CD24- subpopulation with an overall increase in the expression and the number of CD44 + cells. A significant increase in NANOG, SOX2 and SNAI1 expression and enhanced cell migration was observed in claudin-6 transfected cells. Transcriptome analysis revealed 271 genes involved in enhanced biological processes with only 31 with a significantly p value; thirteen of those genes are closely associated to epithelial mesenchymal transition processes and folding and unfolding processes of proteins in the endoplasmic reticulum.

Conclusions

The pro-tumorigenic effect of claudin-6 in gastric cancer could be associated to dedifferentiation of epithelial cells and an increase in di novo cancer stem cell genesis.

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Acknowledgements

Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) grants IN218019 and IN221519, and Programa de Becas Posdoctorales DGAPA-UNAM, Universidad Nacional Autónoma de México, México, supported this work.

Funding

DGAPA-PAPIIT,IN218019,Erika Patricia Rendón-Huerta,IN221519,Luis F Montaño

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Authors and Affiliations

  1. Laboratorio de Inmunobiología, Departamento Biología Celular Y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, México

    Priscila Anhel Medrano-Gonzálezl, Franklin Cruz-Villegas, Alejandro Alarcón del Carmen, Luis Felipe Montaño & Erika Patricia Rendón-Huerta

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  1. Priscila Anhel Medrano-Gonzálezl
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  2. Franklin Cruz-Villegas
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  3. Alejandro Alarcón del Carmen
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by PAM-G, FC-V, and AAdC. The first draft of the manuscript was written by LFM and EPRH and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Erika Patricia Rendón-Huerta.

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Medrano-Gonzálezl, P.A., Cruz-Villegas, F., Alarcón del Carmen, A. et al. Claudin-6 increases SNAI1, NANOG and SOX2 gene expression in human gastric adenocarcinoma AGS cells. Mol Biol Rep 49, 11663–11674 (2022). https://doi.org/10.1007/s11033-022-07976-z

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