ArticleJournal of hematology & oncology2018
Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer tamoxifen resistance in breast cancer.
Article in Journal of hematology & oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
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- Deacetylation of ANXA2 by SIRT2 desensitizes hepatocellular carcinoma cells to donafenib via promoting protective autophagy.Cell death and differentiation · 2025Article
- Overexpression of KIF2C amplifies tamoxifen resistance and lung metastasis of breast cancer through PLK1/C-Myc pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- HOXB13 in cancer development: molecular mechanisms and clinical implications.Frontiers of medicine · 2025Review
- Acetylation: a new target for protein degradation in cancer.Trends in cancer · 2025Review
- P2YActa pharmaceutica Sinica. B · 2025Article
- Multiple regulatory mechanisms, functions and therapeutic potential of chaperone-mediated autophagy.Theranostics · 2025Review
- Reversible Acetylation of Non-histone Proteins in Human Cancers.Results and problems in cell differentiation · 2025Review
- Yiqi Huayu Jiedu Decoction reduces colorectal cancer liver metastasis by promoting N1 neutrophil chemotaxis.Frontiers in immunology · 2025Article
- Her2 promotes early dissemination of breast cancer by inhibiting the p38 pathway through the downregulation of MAP3K4.Cell communication and signaling : CCS · 2024Article
- Compared Inhibitory Activities of Tamoxifen and Avenanthramide B on Liver Esterase and Correlation Based on the Superimposed Structure Between Porcine and Human Liver Esterase.International journal of molecular sciences · 2024Article
- Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.Acta pharmacologica Sinica · 2024Article
- HBXIP induces PARP1 via WTAP-mediated mActa pharmacologica Sinica · 2024Article
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- Research progress on oncoprotein hepatitis B X‑interacting protein (Review).Molecular medicine reports · 2024Review
- Targeting the PD-L1 cytoplasmic domain and its regulatory pathways to enhance cancer immunotherapy.Journal of molecular cell biology · 2024Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to tamoxifen (TAM) frequently occurs in the treatment of estrogen receptor positive (ER+) breast cancer. Accumulating evidences indicate that transcription factor HOXB13 is of great significance in TAM resistance. However, the regulation of HOXB13 in TAM-resistant breast cancer remains largely unexplored. Here, we were interested in the potential effect of HBXIP, an oncoprotein involved in the acceleration of cancer progression, on the modulation of HOXB13 in TAM resistance of breast cancer.
methodsThe Kaplan-Meier plotter cancer database and GEO dataset were used to analyze the association between HBXIP expression and relapse-free survival. The correlation of HBXIP and HOXB13 in ER+ breast cancer was assessed by human tissue microarray. Immunoblotting analysis, qRT-PCR assay, immunofluorescence staining, Co-IP assay, ChIP assay, luciferase reporter gene assay, cell viability assay, and colony formation assay were performed to explore the possible molecular mechanism by which HBXIP modulates HOXB13. Cell viability assay, xenograft assay, and immunohistochemistry staining analysis were utilized to evaluate the effect of the HBXIP/HOXB13 axis on the facilitation of TAM resistance in vitro and in vivo.
resultsThe analysis of the Kaplan-Meier plotter and the GEO dataset showed that mono-TAM-treated breast cancer patients with higher HBXIP expression levels had shorter relapse-free survivals than patients with lower HBXIP expression levels. Overexpression of HBXIP induced TAM resistance in ER+ breast cancer cells. The tissue microarray analysis revealed a positive association between the expression levels of HBXIP and HOXB13 in ER+ breast cancer patients. HBXIP elevated HOXB13 protein level in breast cancer cells. Mechanistically, HBXIP prevented chaperone-mediated autophagy (CMA)-dependent degradation of HOXB13 via enhancement of HOXB13 acetylation at the lysine 277 residue, causing the accumulation of HOXB13. Moreover, HBXIP was able to act as a co-activator of HOXB13 to stimulate interleukin (IL)-6 transcription in the promotion of TAM resistance. Interestingly, aspirin (ASA) suppressed the HBXIP/HOXB13 axis by decreasing HBXIP expression, overcoming TAM resistance in vitro and in vivo.
conclusionsOur study highlights that HBXIP enhances HOXB13 acetylation to prevent HOXB13 degradation and co-activates HOXB13 in the promotion of TAM resistance of breast cancer. Therapeutically, ASA can serve as a potential candidate for reversing TAM resistance by inhibiting HBXIP expression.
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