ArticleOncogene2022
CDK7/GRP78 signaling axis contributes to tumor growth and metastasis in osteosarcoma.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- Chondroitin sulfate shapes the unfolded protein response in osteosarcoma to sustain cancer cell survival during ER stress.Cell death & disease · 2026Article
- A novel MMP13 frameshift variant causes short stature via enhanced MMP13-HSPA5 interaction and activated endoplasmic reticulum stress.Clinical and translational medicine · 2026Article
- Ginkgetin targets GRP78 to induce dual pathways of ER stress and immune activation in osteosarcoma.Oncogene · 2026Article
- Ubiquitination-based Classification and a Prognostic Signature Identify the Role of TRIM21 in Sarcoma Progression.Current medicinal chemistry · 2026Article
- Pyrotinib targeted EGFR/GRP78 mediated cell apoptosis in high EGFR gene copy number gastric cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Deciphering 17-β-hydroxysteroid dehydrogenase 4: from molecular insights to cancer therapeutics.Cancer cell international · 2025Review
- Single-cell analysis links DCUN1D5 to immune remodeling and cisplatin resistance in recurrent osteosarcoma.Communications biology · 2025Article
- AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5.Cell death & disease · 2025Article
- ATF6α inhibits ΔNp63α expression to promote breast cancer metastasis by the GRP78-AKT1-FOXO3a signaling.Cell death & disease · 2025Article
- Tongguanteng injection exerts anti-osteosarcoma effects through the ER stress-associated IRE1/CHOP pathway.BMC complementary medicine and therapies · 2024Article
- Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.Cancer biology & medicine · 2024Review
- Recruitment of USP10 by GCS1 to deubiquitinate GRP78 promotes the progression of colorectal cancer via alleviating endoplasmic reticulum stress.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas.Frontiers in oncology · 2024Review
- Research progress on the GRP78 gene in the diagnosis, treatment and immunity of cervical cancer.European journal of medical research · 2023Review
- A human pan-cancer system analysis of heat shock protein family A member 5.American journal of cancer research · 2023Article
- New progresses on cell surface protein HSPA5/BiP/GRP78 in cancers and COVID-19.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma derives from primitive bone-forming mesenchymal cells and is the most common primary bone malignancy. Therapeutic targeting of osteosarcoma has been unsuccessful; therefore, identifying novel osteosarcoma pathogenesis could offer new therapeutic options. CDK7 is a subunit within the general transcription factor TFIIH. We aim to explore the new mechanism by which CDK7 regulates osteosarcoma and our studies may provide new theoretical support for the use of CDK7 inhibitors in the treatment of osteosarcoma. Here, we investigate the molecular mechanism underlying the association between CDK7 and GRP78 in osteosarcoma. Specifically, we find that an E3 ubiquitin ligase TRIM21 binds and targets GRP78 for ubiquitination and degradation, whereas CDK7 phosphorylates GRP78 at T69 to inhibit TRIM21 recruitment, leading to GRP78 stabilization. Notably, a CDK7-specific inhibitor, THZ1, blunts osteosarcoma growth and metastasis. Combination treatment with CDK7 and GRP78 inhibitors yield additive effects on osteosarcoma growth and progression inhibition. Thus, simultaneous suppression of CDK7 and GRP78 activity represents a potential new approach for the treatment of osteosarcoma. In conclusion, the discovery of this previously unknown CDK7/GRP78 signaling axis provides the molecular basis and the rationale to target human 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 OpenQuestion graph.