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- W2879968231 abstract "Abstract The Nkx2-1 transcription factor promotes differentiation of lung epithelial lineages and suppresses malignant progression of lung adenocarcinoma. However, targets of Nkx2-1 that limit tumor growth and progression remain incompletely understood. Here, direct Nkx2-1 targets are identified whose expression correlates with Nkx2-1 activity in human lung adenocarcinoma. Selenium-binding protein 1 (Selenbp1), an Nkx2-1 effector that limits phenotypes associated with lung cancer growth and metastasis, was investigated further. Loss- and gain-of-function approaches demonstrate that Nkx2-1 is required and sufficient for Selenbp1 expression in lung adenocarcinoma cells. Interestingly, Selenbp1 knockdown also reduced Nkx2-1 expression and Selenbp1 stabilized Nkx2-1 protein levels in a heterologous system, suggesting that these genes function in a positive feedback loop. Selenbp1 inhibits clonal growth and migration and suppresses growth of metastases in an in vivo transplant model. Genetic inactivation of Selenbp1, using CRISPR/Cas9, also enhanced primary tumor growth in autochthonous lung adenocarcinoma mouse models. Collectively, these data demonstrate that Selenbp1 is a direct target of Nkx2-1, which inhibits lung adenocarcinoma growth in vivo. Implications: Selenbp1 is an important suppressor of lung tumor growth that functions in a positive feedback loop with Nkx2-1, and whose loss is associated with worse patient outcome. Mol Cancer Res; 16(11); 1737–49. ©2018 AACR." @default.
- W2879968231 created "2018-07-19" @default.
- W2879968231 creator A5021909111 @default.
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- W2879968231 creator A5079413885 @default.
- W2879968231 creator A5082617119 @default.
- W2879968231 date "2018-11-01" @default.
- W2879968231 modified "2023-09-30" @default.
- W2879968231 title "Tumor Suppressor Activity of Selenbp1, a Direct Nkx2-1 Target, in Lung Adenocarcinoma" @default.
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- W2879968231 doi "https://doi.org/10.1158/1541-7786.mcr-18-0392" @default.
- W2879968231 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6541221" @default.
- W2879968231 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30002193" @default.
- W2879968231 hasPublicationYear "2018" @default.
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