ArticleCell death & disease2019
HACE1 is a potential tumor suppressor in osteosarcoma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Cellular functions and molecular mechanisms of ubiquitination in osteosarcoma.Frontiers in oncology · 2022Pooled it
- Landscape of the Epstein-Barr virus-host chromatin interactome and gene regulation.The EMBO journal · 2025Article
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- LINC00161 upregulated by M2-like tumor-associated macrophages promotes hepatocellular carcinoma progression by methylating HACE1 promoters.Cytotechnology · 2024Article
- Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.Cancer biology & medicine · 2024Review
- A Missense Variant inGenes · 2024Article
- Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.Journal of Cancer · 2024Article
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- Article
- Review
- Ubiquitylation of cyclin C by HACE1 regulates cisplatin-associated sensitivity in gastric cancer.Clinical and translational medicine · 2022Article
- Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA.Cell death & disease · 2021Article
- A novel tumor doubling time-related immune gene signature for prognosis prediction in hepatocellular carcinoma.Cancer cell international · 2021Article
- Article
- Structural Insights into Ankyrin Repeat-Containing Proteins and Their Influence in Ubiquitylation.International journal of molecular sciences · 2021Review
- Adaptation of the Golgi Apparatus in Cancer Cell Invasion and Metastasis.Frontiers in cell and developmental biology · 2021Review
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
- WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an mCell death & disease · 2020Article
- HACE1 Prevents Lung Carcinogenesis via Inhibition of RAC-Family GTPases.Cancer research · 2020Article
- Extracellular Collagen Mediates Osteosarcoma Progression Through an Integrin α2β1/JAK/STAT3 Signaling Pathway.Cancer management and research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Osteosarcoma is a malignant bone sarcoma characterized by extensive genomic disruption and a propensity for metastatic spread. Osteoid production suggests a close relationship with normal osteoblasts, and the latter are the presumptive cell of origin of this disease. The HACE1 gene, localized to human chromosome 6q21, encodes the HACE1 HECT E3 ligase, a tumor suppressor in diverse tumors that acts in part by targeting the activated form of RAC1 GTPase for proteasomal degradation. Disruption or loss of 6q21 is relatively common in osteosarcomas, and Hace1-/-/Tp53+/- mice frequently develop osteosarcomas, in contrast to Tp53+/- mice, which do not. This suggests an unexplored link between HACE1 loss and osteosarcoma. Here we compared HACE1 expression in normal osteoblasts and osteosarcoma cell lines in vitro by western blotting and quantitative RT-PCR, and in human osteosarcoma specimens by immunohistochemistry. Both HACE1 transcript and protein levels were reduced in osteosarcoma compared to osteoblasts in vitro. Reduced HACE1 expression in osteosarcoma tumors was observed in 76% of cases and associated with high-grade lesions. Further, clonally derived pairs of high and low metastatic osteosarcoma cell lines showed significant downregulation in the high compared to corresponding low metastatic cells. Ectopic expression of HACE1 markedly inhibited anchorage-independent growth and cell motility of HACE1 osteosarcoma cell lines, and was associated with reduced RAC1 activation and decreased reactive oxygen species (ROS). Finally, HACE1 overexpression blocked osteosarcoma xenograft growth and dramatically reduced pulmonary metastases. These findings point to a potential tumor suppressor function for HACE1 in osteosarcoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.