ArticleClinical and translational medicine2020
CD13 promotes hepatocellular carcinogenesis and sorafenib resistance by activating HDAC5-LSD1-NF-κB oncogenic signaling.
Article in Clinical and translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
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- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- WNT signalling promotes NF-κB activation and drug resistance in KRAS-mutant colorectal cancer.EMBO reports · 2025Article
- [Mechanistic research progress on radiotherapy resistance of cancer stem cells].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- P4HA2 promotes the progression of papillary thyroid cancer by enhancing degradation of IκBα to activate NF-κB signaling pathway.Cancer cell international · 2025Article
- Mechanisms underlying hepatocellular carcinoma progression through N6-methyladenosine modifications of long non-coding RNA.World journal of gastroenterology · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- HDAC5, an early osimertinib-responsive gene, is a novel therapeutic target for the drug resistance inBiochemistry and biophysics reports · 2025Article
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- Reversible Acetylation of Non-histone Proteins in Human Cancers.Results and problems in cell differentiation · 2025Review
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Saikosaponin D Mitigates Radioresistance in Triple-Negative Breast Cancer by Inducing MRE11 De-Lactylation via HIF1α/HDAC5 Pathway.Theranostics · 2025Article
- MicroRNA Profiling of PRELI-Modulated Exosomes and Effects on Hepatic Cancer Stem Cells.International journal of molecular sciences · 2024Article
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
Abstract
rationaleCD13 is a new marker for liver cancer stem cells (CSCs) that contributes to sorafenib resistance in hepatocellular carcinoma (HCC). However, the underlying mechanism of CD13 in HCC sorafenib resistance remains enigmatic.
methodsThe expression of CD13 in HCC cell lines and tissues was assayed by RT-PCR, western-blot, and immunohistochemistry staining. Athymic BALB/c nu/nu mice model was used to study the in vivo functions of CD13. Clinical significance of CD13 was evaluated by Kaplan-Meier methods. Cellular proliferation rate was evaluated by cell counting kit-8 cell proliferation assay and colony formation assay. Tunel assay was used to detect cell death ratio. Transwell assay was used to evaluate the motility of cells. Immunoprecipitation (IP), liquid chromatography-mass spectrometry (LC-MS)/MS, and co-IP were applied to investigate potential protein interactions of CD13.
resultsIn this research, we found that CD13 expression was higher in metastatic HCC samples, and its overexpression was predicted worse prognosis for patients after surgical resection. Functionally, CD13 promoted HCC proliferation, invasion, cell cycle progression as well as sorafenib resistance. Mechanistically, CD13 interacted with histone deacetylase5 (HDAC5) to promote its protein stability, thus resulting in HDAC5-mediated lysine-specific demethylase 1 (LSD1) deacetylation and protein stabilization. Consequently, LSD1 decreased the NF-κB catalytic unit p65 methylation that led to p65 protein stability. A CD13 inhibitor ubenimex in combination with sorafenib, suppressed the tumor growth and attenuated the resistance of HCC cells toward sorafenib in patient-derived xenograft models.
conclusionsCD13 promotes HCC progression and induces sorafenib resistance, mainly via interacting with HDAC5 to prevent the degradation of p65 and activate NF-kB signaling pathway. CD13 is a prognostic indicator for HCC patients underwent curative resection as well as a predictor of response to treatment with sorafenib. Our study establishes the new therapeutic potential of targeting CD13-HDAC5-LSD1-NF-κB in HCC.
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