Contrasting functions of the epithelial-stromal interaction 1 gene, in human oral and lung squamous cell cancers

The epithelial-stromal interaction 1 gene (EPSTI1) is known to play multiple roles in the malignant progression of breast cancer and also in some aspects of the immune responses to the tumor. However, the relevance of the gene in the onset/progression of oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LSCC) is not yet known. The present study was aimed at revealing the roles of EPSTI1 in conferring malignant characteristics to OSCC and LSCC, and the underlying mechanisms. Quantitative real-time polymerase chain reaction (PCR) and western blot analyses demonstrated significant upregulation of EPSTI1 in all four OSCC cell lines (HSC2, HSC3, HSC3-M3 and HSC4), and significant downregulation of EPST11 in all three LSCC cell lines (LK-2, EBC-1 and H226) used in the present study, as compared to the expression levels in the corresponding control cell lines. Both knockdown of EPST11 in OSCC and overexpression of the gene in LSCC suppressed cell proliferation, and induced cell-cycle arrest in the G1 phase, with upregulation of p21 and downregulation of CDK2 and cyclin D1. Furthermore, these alterations of EPST11 gene expression in the OSCC and LSCC cell lines suppressed the cell migration ability and reversed the EMT phenotype of the tumor cells. Collectively, while EPSTI1 appears to have oncogenic roles in OSCC, it appears to exert tumor-suppressive roles in LSCC. PCR array analyses revealed some genes whose expression levels were altered along with the modified EPSTI1 expression in both the OSCC and LSCC cell lines. These findings suggest that EPSTI1 may be a therapeutic target for both OSCC and LSCC.

Automated summary

The study revealed the roles of EPSTI1 in conferring malignant characteristics to oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LSCC), with the gene showing oncogenic roles in OSCC and tumor-suppressive roles in LSCC. Additionally, PCR array analyses identified some genes with altered expression levels along with modified EPSTI1 expression in both OSCC and LSCC cell lines, suggesting EPSTI1 may be a therapeutic target for both types of cancer.