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AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma
- Source :
- Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-12 (2021), Signal Transduction and Targeted Therapy
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.
- Subjects :
- musculoskeletal diseases
0301 basic medicine
Cancer Research
IDH1
Mice, Nude
lcsh:Medicine
Bone Neoplasms
medicine.disease_cause
Article
Gene Expression Regulation, Enzymologic
Metastasis
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Bone cancer
Genetics
medicine
Animals
Humans
lcsh:QH301-705.5
neoplasms
Mice, Inbred BALB C
Osteosarcoma
Oncogene
biology
Cell growth
business.industry
lcsh:R
Oncogenes
medicine.disease
Hsp90
Isocitrate Dehydrogenase
Neoplasm Proteins
Up-Regulation
Gene Expression Regulation, Neoplastic
HEK293 Cells
030104 developmental biology
Isocitrate dehydrogenase
lcsh:Biology (General)
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
business
Carcinogenesis
Molecular Chaperones
Subjects
Details
- ISSN :
- 20593635
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Signal Transduction and Targeted Therapy
- Accession number :
- edsair.doi.dedup.....582205dd09a271041d3d6f5ff57c6f34