ArticleJournal of experimental & clinical cancer research : CR2022
Targeting TROY-mediated P85a/AKT/TBX3 signaling attenuates tumor stemness and elevates treatment response in hepatocellular carcinoma.
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. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Role of tumor necrosis factor receptor superfamily member 19 in cancer: Diverse functions and therapeutic potential (Review).Oncology letters · 2026Review
- FAT4 loss promotes tumor growth and ferroptosis resistance in hepatocellular carcinoma via PI3K/AKT pathway activation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Unveiling TNFRSF19: a novel tumor suppressor targeting endoplasmic reticulum stress and LGR5/Wnt/β-catenin in cervical cancer.Human cell · 2026Article
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications.Oncology research · 2026Review
- A novel lncRNA-mediated signaling axis governs cancer stemness and splicing reprogramming in hepatocellular carcinoma with therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025Article
- SOX4-ZIP14-zinc metabolism mediates oncogenesis and suppresses T cell immunity in nasopharyngeal carcinoma.Cell reports. Medicine · 2025Article
- DNA-methylation eraser TET2 activates WTIP expression to suppress an AKT-dependent chemoresistance of gastric cancer.Neoplasia (New York, N.Y.) · 2025Article
- Review
- FBF1 maintains stem cell-like properties in breast cancer via PI3K/AKT/SOX2 axis.Stem cell research & therapy · 2025Article
- NIFK, a Potential Prognostic and Immunological Biomarker in Pan-Cancer Analysis, Significantly Regulates Proliferation and Metastasis of Colorectal Cancer.Recent patents on anti-cancer drug discovery · 2025Article
- PFDN6L Gene Predicts Good Prognosis Associated with Its Inhibition of the Stem-Ness Properties in Hepatocellular Carcinoma.Oncology research · 2025Article
- TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance.Theranostics · 2025Article
- The pathogenic germline ETV4 P433L mutation identified in multiple primary lung cancer affect tumor stem-like property by Wnt/β-catenin pathway.Cell death & disease · 2024Article
- Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Context-dependent T-BOX transcription factor family: from biology to targeted therapy.Cell communication and signaling : CCS · 2024Review
- A p85 isoform switch enhances PI3K activation on endosomes by a MAP4- and PI3P-dependent mechanism.Cell reports · 2024Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundPrevious in vitro hepatocyte differentiation model showed that TROY was specifically expressed in liver progenitor cells and a small proportion of hepatocellular carcinoma cells, suggesting that TROY may participate in hepatocellular carcinoma (HCC) stemness regulation. Here, we aim to investigate the role and mechanism of TROY in HCC pathogenesis.
methodBioinformatics analysis of the TCGA dataset has been used to identify the function and mechanism of TROY. Spheroid, apoptosis, and ALDH assay were performed to evaluate the stemness functions. Validation of the downstream pathway was based on Western blot, co-immunoprecipitation, and double immunofluorescence.
resultsHCC tissue microarray study found that a high frequency of TROY-positive cells was detected in 53/130 (40.8%) of HCC cases, which was significantly associated with poor prognosis and tumor metastasis. Functional studies revealed that TROY could promote self-renewal, drug resistance, tumorigenicity, and metastasis of HCC cells. Mechanism study found that TROY could interact with PI3K subunit p85α, inducing its polyubiquitylation and degradation. The degradation of p85α subsequently activate PI3K/AKT/TBX3 signaling and upregulated pluripotent genes expression including SOX2, NANOG, and OCT4, and promoted EMT in HCC cells. Interestingly, immune cell infiltration analysis found that upregulation of TROY in HCC tissues was induced by TGF-β1 secreted from CAFs. PI3K inhibitor wortmannin could effectively impair tumor stemness to sorafenib.
conclusionWe demonstrated that TROY is an HCC CSC marker and plays an important role in HCC stemness regulation. Targeting TROY-positive CSCs with PI3K inhibitor wortmannin combined with chemo- or targeted drugs might be a novel therapeutic strategy for HCC patients.
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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.