ArticleOncogene2022
T-box transcription factor 19 promotes hepatocellular carcinoma metastasis through upregulating EGFR and RAC1.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 20 citations in OpenAlex.
- Quercetin suppresses the progression of HBV-associated hepatocellular carcinoma by modulating the EGFR signaling pathway.PloS one · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- The role of transcription factor TBX19 in melanoma: a comprehensive bioinformatics analysis and cellular experiments.BMC cancer · 2025Article
- Aquaglyceroporin-7 ameliorates sorafenib resistance and immune evasion in hepatocellular carcinoma through inhibition of lipid accumulation.Cellular and molecular life sciences : CMLS · 2025Article
- Effects of NaCell biochemistry and biophysics · 2025Review
- PPY-Induced iCAFs Cultivate an Immunosuppressive Microenvironment in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Context-dependent T-BOX transcription factor family: from biology to targeted therapy.Cell communication and signaling : CCS · 2024Review
- Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review.Translational cancer research · 2024Review
- SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation.Cancer communications (London, England) · 2024Article
- TBX15 facilitates malignant progression of glioma by transcriptional activation of TXDNC5.iScience · 2024Article
- RAD21: A Key Transcriptional Regulator in the Development of Residual Liver Cancer.Journal of hepatocellular carcinoma · 2024Article
- SNS-023 sensitizes hepatocellular carcinoma to sorafenib by inducing degradation of cancer drivers SIX1 and RPS16.Acta pharmacologica Sinica · 2023Article
- RHO GTPase family in hepatocellular carcinoma.Experimental hematology & oncology · 2022Review
- Classical epithelial-mesenchymal transition (EMT) and alternative cell death process-driven blebbishield metastatic-witch (BMW) pathways to cancer metastasis.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effect of targeted therapy for metastatic hepatocellular carcinoma (HCC) is still unsatisfactory. Exploring the underlying mechanism of HCC metastasis is favorable to provide new therapeutic strategies. T-box (TBX) transcription factor family genes, which are crucial regulators in embryo and organ development, are vital for regulating tumor initiation, growth and metastasis. Here we explored the role of TBX19 in HCC metastasis, which is one of the most upregulated TBX family genes in human HCC tissues. TBX19 expression was markedly upregulated in HCC tissues and elevated TBX19 expression predicted poor prognosis. Overexpression of TBX19 enhanced HCC metastasis through upregulating epidermal growth factor receptor (EGFR) and Rac family small GTPase 1 (RAC1) expression. Downregulation of EGFR and RAC1 inhibited TBX19-mediated HCC metastasis, while upregulation of EGFR and RAC1 restored inhibition of HCC metastasis mediated by TBX19 knockdown. Furthermore, epidermal growth factor (EGF)/EGFR signaling upregulated TBX19 expression via the extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-kB axis. Besides, the combined application of EGFR inhibitor Erlotinib and RAC1 inhibitor NSC23766 markedly inhibited TBX19-mediated HCC metastasis. In HCC cohorts, TBX19 expression was positively associated with EGFR and RAC1 expression. Patients with positive coexpression of TBX19/EGFR or TBX19/RAC1 displayed the poorest prognosis. In conclusion, EGF/EGFR signaling upregulated TBX19 expression via ERK/NF-kB pathway and TBX19 fostered HCC metastasis by enhancing EGFR and RAC1 expression, which formed an EGF-TBX19-EGFR positive feedback loop. Targeting this signaling pathway may offer a potential therapeutic strategy to efficiently restrain TBX19-mediated HCC metastasis.
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