ArticleCancers2021
A Yes-Associated Protein (YAP) and Insulin-Like Growth Factor 1 Receptor (IGF-1R) Signaling Loop Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Hepatitis B Doubly Spliced Protein (HBDSP) Promotes Epithelial-Mesenchymal Transition, Migration, and Invasion via SP1/ETS1-Dependent YAP Activation in Hepatoma Cells.Journal of medical virology · 2026Article
- Review
- TCF12 enhances angiogenesis and affects sorafenib response in liver cancer via HIF-1α interaction.Biomolecules & biomedicine · 2025Article
- Picropodophyllin, an IGF‑1 receptor inhibitor, enhances oxaliplatin efficacy in chemoresistant colorectal cancer HCT116 cells by reducing metastatic potential.Oncology letters · 2025Article
- MYBBP1A‑mediated IGFBP4 promoter methylation promotes epithelial‑mesenchymal transition and metastasis through activation of NOTCH pathway in liver cancer.International journal of oncology · 2025Article
- New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma-Today and Tomorrow.International journal of molecular sciences · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Activating the Hippo pathway by nevadensin overcomes Yap-drived resistance to sorafenib in hepatocellular carcinoma.Discover oncology · 2023Article
- The interplay between IGF-1R signaling and Hippo-YAP in breast cancer stem cells.Cell communication and signaling : CCS · 2023Article
- Article
- Disulfiram/Copper Suppresses Cancer Stem Cell Activity in Differentiated Thyroid Cancer Cells by Inhibiting BMI1 Expression.International journal of molecular sciences · 2022Article
- The role of YAP1 in liver cancer stem cells: proven and potential mechanisms.Biomarker research · 2022Review
- Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights.Frontiers in pharmacology · 2022Review
- Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential.Frontiers in endocrinology · 2022Review
- Therapeutic targets for fibro-inflammation in Graves' orbitopathy.Taiwan journal of ophthalmologyReview
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
The role of a YAP-IGF-1R signaling loop in HCC resistance to sorafenib remains unknown.
methodSorafenib-resistant cells were generated by treating naïve cells (HepG2215 and Hep3B) with sorafenib. Different cancer cell lines from databases were analyzed through the ONCOMINE web server. BIOSTORM-LIHC patient tissues (46 nonresponders and 21 responders to sorafenib) were used to compare YAP mRNA levels. The HepG2215_R-derived xenograft in SCID mice was used as an in vivo model. HCC tissues from a patient with sorafenib failure were used to examine differences in YAP and IGF-R signaling.
resultsPositive associations exist among the levels of YAP, IGF-1R, and EMT markers in HCC tissues and the levels of these proteins increased with sorafenib failure, with a trend of tumor-margin distribution in vivo. Blocking YAP downregulated IGF-1R signaling-related proteins, while IGF-1/2 treatment enhanced the nuclear translocation of YAP in HCC cells through PI3K-mTOR regulation. The combination of YAP-specific inhibitor verteporfin (VP) and sorafenib effectively decreased cell viability in a synergistic manner, evidenced by the combination index (CI).
conclusionA YAP-IGF-1R signaling loop may play a role in HCC sorafenib resistance and could provide novel potential targets for combination therapy with sorafenib to overcome drug resistance in HCC.
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Registered trials
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.