ArticleCellular and molecular gastroenterology and hepatology2020
Inactivation of Transcriptional Repressor Capicua Confers Sorafenib Resistance in Human Hepatocellular Carcinoma.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Chemoresistance and genetic mutations in hepatocellular carcinoma: a pharmacogenomic atlas of 51 patients.BMC cancer · 2026Article
- The repressor Capicua is a barrier to lung tumor development driven by Kras/Trp53 mutations.EMBO molecular medicine · 2025Article
- The CIC::DUX4 oncoprotein maintains DNA integrity through direct regulation of the catalytic subunit of DNA polymerase epsilon (POLE).Oncogene · 2025Article
- Hepatocellular carcinoma drug resistance models.Cancer cell international · 2025Review
- Mint3 as a Molecular Target Activated in the Early Stage of Hepatocarcinogenesis.International journal of molecular sciences · 2025Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Multi-Omic Analysis of CIC's Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic Fidelity.Cancers · 2023Article
- FOXM1 Is a Novel Molecular Target of AFP-Positive Hepatocellular Carcinoma Abrogated by Proteasome Inhibition.International journal of molecular sciences · 2022Article
- Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma.International journal of molecular sciences · 2021Article
- BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment.Cell death & disease · 2021Article
- Establishment of liver tumor cell lines from atherogenic and high fat diet fed hepatitis C virus transgenic mice.Scientific reports · 2021Article
- Liver cancer stem cells: Recent progress in basic and clinical research.Regenerative therapy · 2021Review
- Capicua in Human Cancer.Trends in cancer · 2021Review
- Artesunate Regulates Neurite Outgrowth Inhibitor Protein B Receptor to Overcome Resistance to Sorafenib in Hepatocellular Carcinoma Cells.Frontiers in pharmacology · 2021Article
- TRIM25 promotes Capicua degradation independently of ERK in the absence of ATXN1L.BMC biology · 2020Article
- Incapacitated Capicua in Sorafenib-Resistant HCC.Cellular and molecular gastroenterology and hepatology · 2020Article
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20 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsSorafenib is a multireceptor tyrosine kinase inhibitor that can prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Although most HCC patients who receive sorafenib ultimately show disease progression, it still is unclear whether and how HCC cells acquire chemoresistance during sorafenib treatment in human beings.
methodsWe analyzed surgically resected HCC tissues from a patient who received sorafenib for prevention of HCC recurrence after surgery (Adjuvant Sorafenib for Hepatocellular Carcinoma after Resection or Ablation trial) and established patient-derived HCC cells. Whole-exome sequence analysis was performed to detect mutations in sorafenib-resistant clones. We examined 30 advanced HCC cases immunohistochemically and 140 HCC cases enrolled in the Adjuvant Sorafenib for Hepatocellular Carcinoma after Resection or Ablation trial using microarray analysis to evaluate the association of Capicua Transcriptional Repressor (CIC) status with sorafenib treatment response.
resultsWe found a CIC mutation in recurrent HCC specimens after sorafenib. CIC encodes Capicua, a general sensor of receptor tyrosine kinase signaling. HCC cells established from the recurrent tumor specimen showed chemoresistance to sorafenib in vitro and in vivo. Established sorafenib-resistant Huh1 and Huh7 cell lines showed reduced expression of Capicua without mutations. Immunohistochemical analysis showed that HCC patients with low Capicua expression showed poor overall survival. Microarray analysis showed that the CIC gene signature could predict the preventive effect of adjuvant sorafenib treatment on HCC recurrence. Intriguingly, although CIC knockdown induced sorafenib resistance in HCC cell lines, regorafenib suppressed growth of sorafenib-resistant, Capicua-inactivated HCC cells and inhibited extracellular signal-regulated kinase phosphorylation.
conclusionsEvaluation of Capicua status may be pivotal to predict response to sorafenib, and regorafenib treatment could be effective to treat HCC with functional Capicua impairment.
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