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cFOS-SOX9 Axis Reprograms Bone Marrow-Derived Mesenchymal Stem Cells into Chondroblastic Osteosarcoma

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收录情况： ◇ SCIE

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单位： [1]NCI, Canc & Stem Cell Epigenet Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 3140A, Bethesda, MD 20892 USA [2]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Orthopaed,Wuhan 430070,Hubei,Peoples R China [3]NCI, Canc Genet Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA [4]NHLBI, Transgen Core, NIH, Bldg 10, Bethesda, MD 20892 USA [5]NCI, Anim Models Core Facil, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA [6]NCI, Mol Pathol Unit, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA [7]Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA [8]Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA

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Bone marrow-derived mesenchymal stem cells (BMSCs) are proposed as the cells of origin of several subtypes of osteosarcoma (OS). However, signals that direct BMSCs to form different subtypes of OS are unclear. Here we show that the default tumor type from spontaneously transformed p53 knockout (p53_ KO) BMSCs is osteoblastic OS. The development of this default tumor type caused by p53 loss can be overridden by various oncogenic signals: RAS reprograms p53_ KO BMSCs into undifferentiated sarcoma, AKT enhances osteoblastic OS, while cFOS promotes chondroblastic OS formation. We focus on studying the mechanism of cFOS-induced chondroblastic OS formation. Integrated genome-wide studies reveal a regulatory mechanism whereby cFOS binds to the promoter of a key chondroblastic transcription factor, Sox9, and induces its transcription in BMSCs. Importantly, SOX9 mediates cFOS-induced cartilage formation in chondroblastic OS. In summary, oncogenes determine tumor types derived from BMSCs, and the cFOS-SOX9 axis is critical for chondroblastic OS formation.

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出版当年[2016]版：

大类 | 1 区

医学

小类 | 2 区细胞与组织工程 2 区细胞生物学

最新[2025]版：

大类 | 1 区

医学

小类 | 2 区细胞与组织工程 2 区细胞生物学

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出版当年[2015]版：

Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY

最新[2023]版：

Q1 CELL & TISSUE ENGINEERING Q2 CELL BIOLOGY

影响因子： 5.9 最新[2023版] 5.9 最新五年平均 7.023 出版当年[2015版] 7.027 出版当年五年平均 5.365 出版前一年[2014版] 7.338 出版后一年[2016版]

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第一作者单位： [1]NCI, Canc & Stem Cell Epigenet Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 3140A, Bethesda, MD 20892 USA [7]Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA [8]Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA

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