Abstract 2964: Glutathione S-transferase omega 2 (GSTO2) suppresses the acquisition of the senescent tumor cells phenotype in lung adenocarcinoma

Abstract Cellular senescence is a phenomenon characterized by the cell cycle arrest and the induction of inflammatory responses, and is known to contribute to the development and progression of various diseases. In cancerous tissues, some cancer cells acquire the senescent traits, which are referred to as senescent tumor cells (STCs) and contribute to tumor invasion and metastasis. We have previously demonstrated that the expression of glutathione S-transferase omega 2 (GSTO2), which regulates the glutathione redox balance, is exclusively expressed in cells with regenerative ability such as airway basal cells, Clara cells, and type II alveolar cells in the lungs. Contrastingly, the expression of GSTO2 was completely lost in squamous cell carcinoma of the lung (Cancer Science, 2022); however, we found that some of lung adenocarcinoma expressed GSTO2. In this study, we aimed to clarify the significance of GSTO2 in lung adenocarcinoma, especially in the regulation of senescence and STCs. To examine whether GSTO2 expression affects senescence marker expression, we prepared GSTO2-transfected and mock-transfected lung adenocarcinoma cell line PC-9. Forced GSTO2 expression resulted in significantly reduced expression of senescence markers, such as p21, p53, and p16. We performed double staining for GSTO2 with p16 and confirmed the inverse correlation between them in lung adenocarcinoma tissues, where GSTO2-positive cells tended to express lower p16 level compared with GSTO2-negative cells. Furthermore, GSTO2-transfected PC-9 cells showed lower expression of senescence-associated secretory phenotype factors, such as IL-6, TNFα, and IL-1β than mock-transfected cells. These results suggest that GSTO2 suppresses senescence in lung adenocarcinoma cells. We next examined whether GSTO2 expression affects tumor cell growth because senescence is involved in the cell cycle arrest. Expectedly, MTT assay revealed that GSTO2 overexpression in PC-9 cells significantly promoted cell growth compared with the mock transfected cells. Contrastingly, the scratching assay showed that the cell migration of GSTO2-transfected PC-9 cells was significantly delayed compared with that of the mock-transfected cells. In conclusion, we demonstrated that GSTO2 regulates senescence, resulting in the suppression of cell migration. The expression of GSTO2 in lung adenocarcinoma may contribute to the inhibition of the emergence of STCs, being a cause of invasion and resistance to radiotherapy and chemotherapy. Citation Format: Hiroto Hatano, Ryusuke Sumiya, Teruki Hagiwara, Hiromu Suzuki, Kazuhiko Yamada, Norihiro Kokudo, Yuki Kawamura. Glutathione S-transferase omega 2 (GSTO2) suppresses the acquisition of the senescent tumor cells phenotype in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2964.