NOGOB receptor-mediated RAS signaling pathway is a target for suppressing proliferating hemangioma. JCI Insight 2021 Feb 08;6(3)
Date
01/06/2021Pubmed ID
33400686Pubmed Central ID
PMC7934876DOI
10.1172/jci.insight.142299Scopus ID
2-s2.0-85102090712 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Hu W, Liu Z, Salato V, North PE, Bischoff J, Kumar SN, Fang Z, Rajan S, Hussain MM, Miao QRAuthors
Suresh Kumar PhD Associate Professor in the Pathology department at Medical College of WisconsinPaula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers, Tumor
Cell Cycle Checkpoints
Cell Differentiation
Cell Movement
Cell Proliferation
Gene Expression
Gene Knockdown Techniques
Hemangioma
Humans
In Vitro Techniques
Infant
Male
Mice
Mice, Nude
Neoplastic Stem Cells
Receptors, Cell Surface
Signal Transduction
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
ras Proteins
