Genomics · 2024
STRIP2 is regulated by the transcription factor Sp1 and promotes lung adenocarcinoma progression via activating the PI3K/AKT/mTOR/MYC signaling pathway.
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Pan Junfan, Zhang Yuan, He Liu, Wu Yue, Xiao Weijin, Zhang Jing, Xu Yiquan
Аннотация
BACKGROUND: Patients with lung adenocarcinoma (LUAD) generally have poor prognosis. The role of striatin-interacting protein 2 (STRIP2) in LUAD remain unclear.
METHODS: Liquid chromatography-mass spectrometry analyses were used to screen the STRIP2-binding proteins and co-immunoprecipitation verified these interactions. A dual luciferase reporter assay explored the transcription factor activating STRIP2 transcription. Xenograft and lung metastasis models assessed STRIP2's role in tumor growth and metastasis in vivo.
RESULTS: STRIP2 is highly expressed in LUAD tissues and is linked to poor prognosis. STRIP2 expression in LUAD cells significantly promoted cell proliferation, invasion, and migration in vitro and in vivo. Mechanistically, STRIP2 boosted the PI3K/AKT/mTOR/MYC cascades by binding AKT. In addition, specificity protein 1, potently activated STRIP2 transcription by binding to the STRIP2 promoter. Blocking STRIP2 reduces tumor growth and lung metastasis in xenograft models.
CONCLUSIONS: Our study identifies STRIP2 is a key driver of LUAD progression and a potential therapeutic target.
METHODS: Liquid chromatography-mass spectrometry analyses were used to screen the STRIP2-binding proteins and co-immunoprecipitation verified these interactions. A dual luciferase reporter assay explored the transcription factor activating STRIP2 transcription. Xenograft and lung metastasis models assessed STRIP2's role in tumor growth and metastasis in vivo.
RESULTS: STRIP2 is highly expressed in LUAD tissues and is linked to poor prognosis. STRIP2 expression in LUAD cells significantly promoted cell proliferation, invasion, and migration in vitro and in vivo. Mechanistically, STRIP2 boosted the PI3K/AKT/mTOR/MYC cascades by binding AKT. In addition, specificity protein 1, potently activated STRIP2 transcription by binding to the STRIP2 promoter. Blocking STRIP2 reduces tumor growth and lung metastasis in xenograft models.
CONCLUSIONS: Our study identifies STRIP2 is a key driver of LUAD progression and a potential therapeutic target.
Предметные рубрики MeSH
HumansTOR Serine-Threonine KinasesProto-Oncogene Proteins c-aktLung NeoplasmsAdenocarcinoma of LungAnimalsSignal TransductionPhosphatidylinositol 3-KinasesMiceSp1 Transcription FactorProto-Oncogene Proteins c-mycCell Line, TumorMice, NudeCell ProliferationA549 CellsCell MovementGene Expression Regulation, NeoplasticFemaleMaleDisease Progression