Glutathione peroxidase 8 expression on cancer cells and cancer‐associated fibroblasts facilitates lung cancer metastasis

Abstract

Lung cancer is the leading cause of cancer death worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Metastasis is the major cause of poor prognosis and mortality for lung cancer patients, which urgently needs great efforts to be further explored. Herein, glutathione peroxidase 8 (GPX8) was identified as a novel potential pro‐metastatic gene in LUAD metastatic mice models from GEO database. GPX8 was highly expressed in tumor tissues, predicting poor prognosis in LUAD patients. Knockdown of GPX8 inhibited LUAD metastasis in vitro and in vivo, while it did not obviously affect tumor growth. Knockdown of GPX8 decreased the levels of p‐FAK and p‐Paxillin and disturbed the distribution of focal adhesion. Furthermore, GPX8 was overexpressed in cancer‐associated fibroblast (CAF) and associated with CAF infiltration in tumor microenvironment of lung cancer. GPX8 silence on fibroblasts suppressed lung cancer cell migration in the coculture system. BRD2 and RRD4 were the potential transcriptionally regulators for GPX8. Bromodomain extra‐terminal inhibitor JQ1 downregulated GPX8 expression and suppressed lung cancer cell migration. Our findings indicate that highly expressed GPX8 in lung cancer cells and fibroblasts functions as a pro‐metastatic factor in lung cancer. JQ1 is identified as a potential inhibitor against GPX8‐mediated lung cancer metastasis.

GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment

“…Notably, in a recent study on lung cancer, researchers discovered that GPX8 expression on cancer-associated fibroblasts can promote the metastasis of lung cancer cells [50]. Our findings, corroborated in multiple cohorts, indicate that in LUAD, GPX8 is primarily localized on CAFs.…”

Therapeutic Targeting of Cancer-Associated Fibroblasts in the Non-Small Cell Lung Cancer Tumor Microenvironment

“…JQ1 attenuated the activation of CAFs via the inhibition of Hedgehog and TGF-β pathways [118]. JQ1 also downregulates glutathione peroxidase 8 (GPX8) expression, which is overexpressed in CAFs and is associated with CAF infiltration in the tumor microenvironment of NSCLC [119]. Furthermore, aberrant expression of histone deacetylases (HDACs) is frequent in human cancers and may be involved in the progression of fibrosis in idiopathic pulmonary fibrosis, as well as NSCLC progression [120].…”

Nutrición animal: Texto de formación universitaria

“…La GPx5 se expresa en el tejido del epidídimo, protege los espermatozoides del estrés oxidativo (Chu et al, 2020); la GPx6 solo se expresa en el cuerpo humano. Ambas enzimas, GPx7 y GPx8, se encuentran en el retículo endoplásmico y son enzimas necesarias involucradas en el plegamiento oxidativo de las proteínas del retículo endoplásmico (Pei et al, 2023), y es una enzima metabólica que regula la agresividad del cáncer, en sus distintas formas (Khatib et al, 2020;Ren et al, 2022;Zhang et al, 2020;Xu et al, 2022).…”