NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma
| Autor: | Sujith Rajan, Paula E. North, Wenquan Hu, Joyce Bischoff, Zhi Fang, Suresh Kumar, Qing R Miao, Zhong Liu, M. Mahmood Hussain, Valerie K. Salato |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Angiogenesis Endothelial cells Gene Expression Mice Nude Receptors Cell Surface In Vitro Techniques Cell cycle Signal transduction Vascular biology Hemangioma Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans Involution (medicine) Cell Proliferation Gene knockdown Chemistry Infant Cell Differentiation Cell Cycle Checkpoints General Medicine medicine.disease Xenograft Model Antitumor Assays Cell biology 030104 developmental biology Ras Signaling Pathway Gene Knockdown Techniques 030220 oncology & carcinogenesis Neoplastic Stem Cells ras Proteins Medicine Stem cell Research Article |
| Zdroj: | JCI Insight, Vol 6, Iss 3 (2021) JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | Infantile hemangioma is a vascular tumor characterized by the rapid growth of disorganized blood vessels followed by slow spontaneous involution. The underlying molecular mechanisms that regulate hemangioma proliferation and involution still are not well elucidated. Our previous studies reported that NOGOB receptor (NGBR), a transmembrane protein, is required for the translocation of prenylated RAS from the cytosol to the plasma membrane and promotes RAS activation. Here, we show that NGBR was highly expressed in the proliferating phase of infantile hemangioma, but its expression decreased in the involuting phase, suggesting that NGBR may have been involved in regulating the growth of proliferating hemangioma. Moreover, we demonstrate that NGBR knockdown in hemangioma stem cells (HemSCs) attenuated growth factor–stimulated RAS activation and diminished the migration and proliferation of HemSCs, which is consistent with the effects of RAS knockdown in HemSCs. In vivo differentiation assay further shows that NGBR knockdown inhibited blood vessel formation and adipocyte differentiation of HemSCs in immunodeficient mice. Our data suggest that NGBR served as a RAS modulator in controlling the growth and differentiation of HemSCs. |
| Databáze: | OpenAIRE |
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