ArticleCell death & disease2021
TRIM21-regulated Annexin A2 plasma membrane trafficking facilitates osteosarcoma cell differentiation through the TFEB-mediated autophagy.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Mechanisms of TRIM21-mediated RUNX2 degradation via chaperone-mediated autophagy in periodontitis.Cell biology and toxicology · 2026Article
- TRIM21 contributes to senile osteoporosis by shifting the osteoadipogenic balance toward adipogenesis in BMSCs.Science China. Life sciences · 2026Article
- Ubiquitination-based Classification and a Prognostic Signature Identify the Role of TRIM21 in Sarcoma Progression.Current medicinal chemistry · 2026Article
- ANXA2 in hepatocellular carcinoma: orchestrating tumorigenesis, progression, and therapeutic resistance toward precision targeting.Journal of translational medicine · 2025Review
- TM9SF1 inhibits colorectal cancer metastasis by targeting Vimentin for Tollip-mediated selective autophagic degradation.Cell death and differentiation · 2025Article
- Deacetylation of ANXA2 by SIRT2 desensitizes hepatocellular carcinoma cells to donafenib via promoting protective autophagy.Cell death and differentiation · 2025Article
- Trim21 deficiency alleviates osteoporosis by inhibiting osteoclast differentiation through regulating Txnip.Arthritis research & therapy · 2025Article
- TRIM21-driven K63-linked ubiquitination of RBM38c, as a novel interactor of BECN1, contributes to DNA damage-induced autophagy.Cell death and differentiation · 2025Article
- S100 A16 promotes the progression of osteosarcoma by activating the PI3 K/AKT signaling pathway through ANXA2.Scientific reports · 2025Article
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- FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-α/β expression to impede the progression of lung adenocarcinoma.Cell death & disease · 2025Article
- The osteosarcoma immune microenvironment in progression: PLEK as a prognostic biomarker and therapeutic target.Frontiers in immunology · 2025Article
- PTPRC Inhibits Ferroptosis of Osteosarcoma Cells via Blocking TFEB/FTH1 Signaling.Molecular biotechnology · 2024Article
- The upregulation of Annexin A2 by TLR4 pathway facilitates lipid accumulation and liver injury via blocking AMPK/mTOR-mediated autophagy flux during the development of non-alcoholic fatty liver disease.Hepatology international · 2024Article
- NEK2 contributes to radioresistance in esophageal squamous cell carcinoma by inducing protective autophagy via regulating TRIM21.Cancer cell international · 2024Article
- Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.Cell death & disease · 2024Article
- Article
- ANXA2 (annexin A2) is crucial to ATG7-mediated autophagy, leading to tumor aggressiveness in triple-negative breast cancer cells.Autophagy · 2024Article
- Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization.Bone research · 2023Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and differentiation in OS is largely unknown. In the present study, we first showed that TRIM21 could promote OS cell autophagy, as determined by the accumulation of LC3-II, and the degradation of cargo receptor p62. Further, we were able to identify that Annexin A2 (ANXA2), as a novel interacting partner of TRIM21, was critical for TIRM21-induced OS cell autophagy. Although TRIM21 had a negligible effect on the mRNA and protein expressions of ANXA2, we did find that TRIM21 facilitated the translocation of ANXA2 toward plasma membrane (PM) in OS cells through a manner relying on TRIM21-mediated cell autophagy. This functional link has been confirmed by observing a nice co-expression of TRIM21 and ANXA2 (at the PM) in the OS tissues. Mechanistically, we demonstrated that TRIM21, via facilitating the ANXA2 trafficking at the PM, enabled to release the transcription factor EB (TFEB, a master regulator of autophagy) from the ANXA2-TFEB complex, which in turn entered into the nucleus for the regulation of OS cell autophagy. In accord with previous findings that autophagy plays a critical role in the control of differentiation, we also demonstrated that autophagy inhibited OS cell differentiation, and that the TRIM21/ANXA2/TFEB axis is implicated in OS cell differentiation through the coordination with autophagy. Taken together, our results suggest that the TRIM21/ANXA2/TFEB axis is involved in OS cell autophagy and subsequent differentiation, indicating that targeting this signaling axis might lead to a new clue for OS treatment.
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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.