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CDH4 is a novel determinant of osteosarcoma tumorigenesis and metastasis.
- Source :
-
Oncogene [Oncogene] 2018 Jul; Vol. 37 (27), pp. 3617-3630. Date of Electronic Publication: 2018 Apr 03. - Publication Year :
- 2018
-
Abstract
- The era of cancer genomics now provides an opportunity to discover novel determinants of osteosarcoma (OS), the most common primary bone cancer in children and adolescents known for its poor prognosis due to lung metastasis. Here, we identify CDH4 amplification in 43.6% of human osteosarcoma using array CGH and demonstrate its critical role in osteosarcoma development and progression. Gain or loss-of-function of CDH4, which encodes R-cadherin, causally impacts multiple features of human OS cells including cell migration and invasion, osteogenic differentiation, and stemness. CDH4 overexpression activates c-Jun via the JNK pathway, while CDH4 knockdown suppresses both tumor xenograft growth and lung colonization. In OS patient specimens, high CDH4 expression associates with lung metastases and poor prognosis. Collectively, our bioinformatics, functional, molecular, and clinical analyses uncover an oncogenic function of CDH4 in osteosarcoma and its relationship with patient outcome.
- Subjects :
- Animals
Carcinogenesis genetics
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Female
Gene Expression Regulation, Neoplastic genetics
Humans
JNK Mitogen-Activated Protein Kinases metabolism
Lung Neoplasms secondary
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness genetics
Neoplasm Transplantation
Osteogenesis genetics
RNA Interference
RNA, Small Interfering genetics
Transplantation, Heterologous
Bone Neoplasms genetics
Bone Neoplasms pathology
Cadherins biosynthesis
Cadherins genetics
Osteosarcoma genetics
Osteosarcoma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 37
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 29610525
- Full Text :
- https://doi.org/10.1038/s41388-018-0231-2