ArticleJournal of experimental & clinical cancer research : CR2022
AHSA1 is a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- MAGEC2 promotes tumorigenesis in multiple myeloma through USP16-mediated deubiquitination and stabilization of c-Myc.Experimental hematology & oncology · 2026Article
- Immediate tumor killing and long-term anti-tumor immunoreaction induced by Bufalin-loaded phototherapeutic Janus membrane in CRC postoperative therapy.Materials today. Bio · 2026Article
- Circular RNA circAHSA1 serves as a stable serum biomarker for the diagnosis and progression of gastric cancer.Translational oncology · 2026Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Demystifying programmed cell death in lung adenocarcinoma: combined prognostic model construction.Translational cancer research · 2025Article
- UPP1 and AHSA1 as emerging biomarkers and targets in pancreatic cancer: A proteomic approach.Biomolecules & biomedicine · 2025Article
- AHSA1-HSP90AA1 complex stabilized IFI6 and TGFB1 promotes mitochondrial stability and EMT in EGFR-mutated lung adenocarcinoma under Osimertinib pressure.Cell death & disease · 2025Article
- SAE1 promotes tumor cell malignancyActa pharmaceutica Sinica. B · 2025Article
- A Six-Gene Signature Related to Liquid-Liquid Phase Separation for Diagnosis of Alzheimer's Disease.Actas espanolas de psiquiatria · 2024Article
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- Article
- Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation.Cell death & disease · 2023Article
- Correction: AHSA1 is a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2023Article
- Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs.Molecules (Basel, Switzerland) · 2023Review
- AHSA1 Regulates Hepatocellular Carcinoma Progression via the TGF-β/Akt-Cyclin D1/CDK6 Pathway.Journal of hepatocellular carcinoma · 2023Article
- LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473.Frontiers in oncology · 2023Article
- New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.Acta pharmaceutica Sinica. B · 2022Review
- AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma.Cancers · 2022Article
- Co-occurrence of CDKN2A/B and IFN-I homozygous deletions correlates with an immunosuppressive phenotype and poor prognosis in lung adenocarcinoma.Molecular oncology · 2022Article
- Ginsenosides: Allies of gastrointestinal tumor immunotherapy.Frontiers in pharmacology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrently, multiple myeloma (MM) is still an incurable plasma cell malignancy in urgent need of novel therapeutic targets and drugs.
methodsBufalin was known as a highly toxic but effective anti-cancer compound. We used Bufalin as a probe to screen its potential targets by proteome microarray, in which AHSA1 was the unique target of Bufalin. The effects of AHSA1 on cellular proliferation and drug resistance were determined by MTT, western blot, flow cytometry, immunohistochemistry staining and xenograft model in vivo. The potential mechanisms of Bufalin and KU-177 in AHSA1/HSP90 were verified by co-immunoprecipitation, mass spectrometry, site mutation and microscale thermophoresis assay.
resultsAHSA1 expression was increased in MM samples compared to normal controls, which was significantly associated with MM relapse and poor outcomes. Furthermore, AHSA1 promoted MM cell proliferation and proteasome inhibitor (PI) resistance in vitro and in vivo. Mechanism exploration indicated that AHSA1 acted as a co-chaperone of HSP90A to activate CDK6 and PSMD2, which were key regulators of MM proliferation and PI resistance respectively. Additionally, we identified AHSA1-K137 as the specific binding site of Bufalin on AHSA1, mutation of which decreased the interaction of AHSA1 with HSP90A and suppressed the function of AHSA1 on mediating CDK6 and PSMD2. Intriguingly, we discovered KU-177, an AHSA1 selective inhibitor, and found KU-177 targeting the same site as Bufalin. Bufalin and KU-177 treatments hampered the proliferation of flow MRD-positive cells in both primary MM and recurrent MM patient samples. Moreover, KU-177 abrogated the cellular proliferation and PI resistance induced by elevated AHSA1, and decreased the expression of CDK6 and PSMD2.
conclusionsWe demonstrate that AHSA1 may serve as a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma.
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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.