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Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells.
- Source :
-
Scientific reports [Sci Rep] 2018 Oct 08; Vol. 8 (1), pp. 14913. Date of Electronic Publication: 2018 Oct 08. - Publication Year :
- 2018
-
Abstract
- BMP4/7-dependent expression of inhibitor of differentiation/DNA binding (Id) proteins 1 and 3 has been implicated in tumor progression and poor prognosis of malignant melanoma patients. Hyaluronic acid (HA), a pericellular matrix component, supports BMP7 signalling in murine chondrocytes through its receptor CD44. However, its role in regulating BMP signalling in melanoma is not clear. In this study we found that depletion of endogenously-produced HA by hyaluronidase treatment or by inhibition of HA synthesis by 4-methylumbelliferone (4-MU) resulted in reduced BMP4/7-dependent Id1/3 protein expression in mouse melanoma B16-F10 and Ret cells. Conversely, exogenous HA treatment increased BMP4/7-dependent Id1/3 protein expression. Knockdown of CD44 reduced BMP4/7-dependent Id1/3 protein expression, and attenuated the ability of exogenous HA to stimulate Id1 and Id3 expression in response to BMP. Co-IP experiments demonstrated that CD44 can physically associate with the BMP type II receptor (BMPR) ACVR2B. Importantly, we found that coordinate expression of Id1 or Id3 with HA synthases HAS2, HAS3, and CD44 is associated with reduced overall survival of cutaneous melanoma patients. Our results suggest that HA-CD44 interactions with BMPR promote BMP4/7-dependent Id1/3 protein expression in melanoma, contributing to reduced survival in melanoma patients.
- Subjects :
- Animals
Bone Morphogenetic Protein 4 genetics
Bone Morphogenetic Protein 7 genetics
Humans
Hyaluronan Receptors genetics
Hyaluronic Acid genetics
Inhibitor of Differentiation Protein 1 genetics
Inhibitor of Differentiation Proteins genetics
Melanoma, Experimental genetics
Melanoma, Experimental pathology
Mice
Neoplasm Proteins genetics
Skin Neoplasms genetics
Skin Neoplasms pathology
Bone Morphogenetic Protein 4 biosynthesis
Bone Morphogenetic Protein 7 biosynthesis
Gene Expression Regulation, Neoplastic
Hyaluronan Receptors metabolism
Hyaluronic Acid metabolism
Inhibitor of Differentiation Protein 1 biosynthesis
Inhibitor of Differentiation Proteins biosynthesis
Melanoma, Experimental metabolism
Neoplasm Proteins metabolism
Skin Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 30297743
- Full Text :
- https://doi.org/10.1038/s41598-018-33337-7