FOXA3 regulates cholesterol metabolism to compensate for low uptake during the progression of lung adenocarcinoma

• DOI: 10.1371/journal.pbio.3002621
• Publication Date: 2024-05-28T18:41:55Z
• Authors: Dongmei Wang; Yuxiang Cao; Meiyao Meng; Jin Qiu; Chao Ni; Xiaozhen Guo; Yu Li; Shuang Liu; Jian Yu; Mingwei Guo; Jiawen Wang; Bing Du; Wenwei Qiu; Cen Xie; Bing Zhao; Xinran Ma; Xinghua Cheng; Lingyan Xu
• Keywords: 0303 health sciences; 03 medical and health sciences; Research Article

Cholesterol metabolism is vital for multiple cancer progression, while how cholesterol affects lung, a low-cholesterol tissue, metastasis and the underlying mechanism remain unclear. In this study, we found that metastatic lung adenocarcinoma cells acquire cellular dehydrocholesterol by endogenous biosynthesis, instead of uptake upon treatment. Besides, demonstrated exogenous functions as signaling molecule to induce FOXA3, key transcription factor lipid via GLI2. Subsequently, ChIP-seq analysis molecular studies revealed FOXA3 transcriptionally activated Hmgcs1, an essential enzyme level membrane composition change cell migration. Conversely, knockdown or knockout blocked biosynthesis in mice. addition, potent inhibitor magnolol suppressed gene programs patient-derived organoids (PDOs). Altogether, our findings shed light onto unique contribution metastasis.