Abstract 2580: Contrasting functions of EPSTI1 in human oral and lung squamous cell cancer cell lines - its tumor promoting roles in oral and tumor suppressing roles in lung squamous cell carcinomas

Abstract

Abstract Introduction: Epithelial-stromal interaction 1 (EPSTI1) is a gene mapped to human chromosome 13q13.3. Recent studies have shown that EPSTI1 regulates many malignant features of cancers. However, the relevance of EPSTI1 to oral squamous cell carcinomas (OSCC) and lung squamous cell carcinoma (LSCC) are not known. The present study aimed to uncover the roles and the underlying mechanisms of EPSTI1 in OSCC and LSCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were used to evaluate the expression of EPSTI1 in four OSCC cell lines, HSC2, HSC3, HSC3M3 and HSC4, and three LSCC cell lines, LK-2, EBC-1 and H226. In vitro experiments were carried out in parental, their shRNA EPSTI1 knockdown and EPSTI1 overexpressing cells. Cell cycle was evaluated by flow cytometry, and epithelial-to-mesenchymal transition (EMT)-related proteins were evaluated by western blot assay. Changes in expression of EPSTI1-related genes in transfected cells were confirmed by using RT2 Profiler PCR Array Human Cancer Pathway Finder. Results: EPSTI1 was significantly up-regulated in OSCC cell lines, and significantly down-regulated in LSCC cell lines compared to their normal counterparts. Knockdown of EPSTI1 in OSCC cells and overexpression of the gene in LSCC cells suppressed cell proliferation accompanied by cell-cycle arrest in the G1 phase with up-regulation of p21 and down-regulation of CDK2 and cyclin D1. These indicate that EPSTI1 was significantly involved in tumor growth in OSCC and LSCC, but in an opposite direction. Furthermore, EPSTI1 was related to enhanced cell migration and EMT phenotype in OSCC, and it was related to suppressed cell migration and reversed EMT in LSCC. In PCR-array analyses in two OSCC and two LSCC cells, some common genes were regulated similarly in each OSCC and LSCC. Conclusion: EPSTI1 was up-regulated and its down-regulation suppressed the malignant phenotypes, indicating oncogenic roles of the gene in OSCC. In contrast the gene was down-regulated and its up-regulation suppressed the malignant phenotypes, indicating tumor suppressive roles of the gene in LSCC. These findings suggest that EPSTI1 might be a therapeutic target for OSCC and LSCC. Citation Format: Meng Meng Fan, Makoto Arai, Akinobu Tawada, Tetsuhiro Chiba, Reo Fukushima, Katsuhiro Uzawa, Masashi Shiiba, Naoya Kato, Hideki Tanzawa, Yuichi Takiguchi. Contrasting functions of EPSTI1 in human oral and lung squamous cell cancer cell lines - its tumor promoting roles in oral and tumor suppressing roles in lung squamous cell carcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2580.