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PTGFRN promotes non-small cell lung cancer malignant progression and reprograms BCAA metabolism by activating
Feiye Liu1, Mengjie Li2, Peng Yu3
1Respiratory Department of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Fuoshan, Guangdong 528042, China; Oncology Center of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Fuoshan, Guangdong 528042, China.
Abstract:
Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein that has been linked to the metastatic behavior of certain cancers. However, its specific function and underlying regulatory mechanisms in lung cancer remain unclear. In this research, we observed that PTGFRN expression was markedly increased in lung cancer tissues compared to normal tissues, and patients with high PTGFRN levels exhibited poorer survival outcomes. Silencing PTGFRN significantly inhibited non-small cell lung cancer cell proliferation, tumor formation, and metastatic capacity. Mechanistically, PTGFRN was found to interact with signal transducer and activator of transcription 3 (STAT3)and inhibit its degradation. The resulting accumulation of STAT3 enhanced its binding to the BCAT1 gene promoter, thereby boosting branched-chain amino acid transaminase 1 (BCAT1) expression. This subsequently elevated branched-chain amino acid (BCAA) metabolism in lung cancer cells. Overall, our findings highlight the tumor-promoting role of PTGFRN in non-small cell lung cancer and demonstrate that PTGFRN accelerates cancer progression by enhancing the STAT3/BCAT1 signaling axis and reprogramming BCAA metabolism.
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