Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma

Abstract

Glutathione S-transferase omega 2 (GSTO2) lacks any appreciable GST activity, but it exhibits thioltransferase activity. The significance of GSTO2 in lung function has been reported; however, the precise expression and molecular function of GSTO2 in the lungs remain unclear. In the present study, we found that GSTO2 is expressed in airway basal cells, non-ciliated, columnar Clara cells, and type II alveolar cells, which have self-renewal capacity in the lungs. Contrastingly, no GSTO2 expression was observed in 94 lung squamous cell carcinoma (LSCC) samples. When human LSCC cell lines were treated with 5-aza-2′-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant GSTO2 hypermethylation in LSCC is the cause of its downregulation. Forced GSTO2 expression in How to cite this article: Sumiya R, Terayama M, Hagiwara T, et al. Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma.

ProstaMine: a bioinformatics tool for identifying subtype-specific co-alterations associated with aggressiveness in prostate cancer

“…The third ranked single gene hit identified by ProstaMine was GSTO2 , followed by SMAD4 and MT1M , which were ranked sixth and eighth, respectively. GSTO2 and MT1M have been described as tumor suppressors in cancer, and SMAD4 is listed as a tumor suppressor gene in the COSMIC Cancer Gene Census ( Mao et al, 2012 ; Sondka et al, 2018 ; Terayama et al, 2020 ; Xu et al, 2020 ; Li et al, 2021 , 2023; Sumiya et al, 2022 ) . GSTO2 and MT1M functions have not been reported as factors in PCa progression, whereas loss of SMAD4 function has been shown to drive tumor growth and metastasis ( Ding et al, 2011 ).…”

“…GSTO2 encodes a glutathione transferase involved in cellular detoxification. GSTO2 functions as a tumor suppressor through p38-mediated MAPK signaling in esophageal and squamous skin cell carcinoma ( Terayama et al, 2020 ; Sumiya et al, 2022 ) . SMAD4 encodes a transcription factor serving as the central regulator of the TGFb-activated and BMP4-activated SMAD signaling pathways.…”

Exome‐based genome‐wide screening of rare variants associated with the risk of polycystic ovary syndrome

“… 2 , 4 Since the dehydroascorbate reductase activity of GSTO2 is approximately 70–100‐fold higher than that of GSTO1, GSTO2 may play a more protective role against oxidative stress than GSTO1. 32 Furthermore, because GSTO2 has been implicated in p38 phosphorylation, 33 which is essential for ER stress, 34 GSTO2 variants may increase the risk of PCOS through aberrant ER stress. However, the clinical significance of the GSTO2 variants identified in this study needs to be confirmed in future studies.…”