HOXB13 controls cell state through super-enhancers

Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tum...

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Bibliographic Details
Published in:Experimental cell research 2020-08, Vol.393 (1), p.112039-112039, Article 112039
Main Authors: Aspuria, Paul-Joseph, Cheon, Dong-Joo, Gozo, Maricel C., Beach, Jessica A., Recouvreux, Maria Sol, Walts, Ann E., Karlan, Beth Y., Orsulic, Sandra
Format: Article
Language:English
Subjects:
Adipogenesis
Bone and Bones - metabolism
Cell Differentiation - genetics
Cell Differentiation - physiology
Differentiation
Gene Expression Regulation - genetics
Genes, Homeobox - genetics
Homeobox
Homeodomain Proteins - metabolism
HOXB13
Humans
Mesenchymal stem cells
Mesenchymal Stem Cells - cytology
Myogenesis
Osteogenesis
Osteogenesis - physiology
Rhabdoid tumor
Sarcoma
Super-enhancer
Transcription Factors - metabolism
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Summary:Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tumor. In a xenograft model of rhabdoid tumor, knockout of HOXB13 diminished tumor growth while partial knockdown of HOXB13 promoted differentiation of tumor cells into bone. These results suggest that HOXB13 enhances rhabdoid malignancy by interfering with mesenchymal stem cell differentiation. Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. Mechanistically, we demonstrated that HOXB13 binds to super-enhancer regions regulating genes involved in differentiation and tumorigenesis. [Display omitted] •HOXB13 is aberrantly overexpressed in poorly differentiated sarcomas.•Knockdown of HOXB13 in a rhabdoid tumor xenograft leads to osteogenic differentiation.•Overexpression of HOXB13 inhibits differentiation of mesenchymal progenitor cells.•HOXB13 is a master transcription factor that regulates genes involved in cell state.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2020.112039