ArticleJournal of experimental & clinical cancer research : CR2022
PITX2C increases the stemness features of hepatocellular carcinoma cells by up-regulating key developmental factors in liver progenitor.
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 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- ELYS promotes hepatocellular carcinoma stemness by activating a FOXO6-NUP205 transcriptional module downstream of PI3K/AKT to drive Hedgehog signaling.Cell & bioscience · 2026Article
- TFAP2A enhances tumor stemness and promotes metastasis in pancreatic ductal adenocarcinoma.iScience · 2025Article
- Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function by inducing apoptosis in a rat model of experimental autoimmune prostatitis.International journal of impotence research · 2025Article
- Radiomic features at contrast-enhanced CT predict proliferative hepatocellular carcinoma and its prognosis after transarterial chemoembolization.Scientific reports · 2025Article
- RALYL Overexpression Suppresses Colorectal Cancer via Modulating HNRNPC-Mediated MNK2 Alternative Splicing.Cancer reports (Hoboken, N.J.) · 2025Article
- Tumour heterogeneity and personalized treatment screening based on single-cell transcriptomics.Computational and structural biotechnology journal · 2025Article
- Multi-omics landscape of alternative splicing in diffuse midline glioma reveals immune- and neural-driven subtypes with implications for spliceosome-targeted therapy.Frontiers in immunology · 2025Article
- Regulatory factor X-5/SCL/TAL1 interruption site axis promotes aerobic glycolysis and hepatocellular carcinoma cell stemness.The Kaohsiung journal of medical sciences · 2025Article
- Follow-up value of serum AFP and aminotransferases in chronic hepatitis B progression.Frontiers in cellular and infection microbiology · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTumor cells exhibited phenotypic and molecular characteristics similar to their lineage progenitor cells. Liver developmental signaling pathways are showed to be associated with HCC development and oncogenesis. The similarities of expression profiling between liver progenitors (LPs) and HCC suggest that understanding the molecular mechanism during liver development could provide insights into HCC.
methodsTo profile the dynamic gene expression during liver development, cells from an in vitro liver differentiation model and two paired hepatocellular carcinoma (HCC) samples were analyzed using deep RNA sequencing. The expression levels of selected genes were analyzed by qRT-PCR. Moreover, the role of a key transcription factor, pituitary homeobox 2 (PITX2), was characterized via in vitro and vivo functional assays. Furthermore, molecular mechanism studies were performed to unveil how PITX2C regulate the key developmental factors in LPs, thereby increasing the stemness of HCC.
resultsPITX2 was found to exhibit a similar expression pattern to specific markers of LPs. PITX2 consists of three isoforms (PITX2A/B/C). The expression of PITX2 is associated with tumor size and overall survival rate, whereas only PITX2C expression is associated with AFP and differentiation in clinical patients. PITX2A/B/C has distinct functions in HCC tumorigenicity. PITX2C promotes HCC metastasis, self-renewal and chemoresistance. Molecular mechanism studies showed that PITX2C could up-regulate RALYL which could enhance HCC stemness via the TGF-β pathway. Furthermore, ChIP assays confirmed the role of PITX2C in regulating key developmental factors in LP.
conclusionPITX2C is a newly discovered transcription factor involved in hepatic differentiation and could increase HCC stemness by upregulating key transcriptional factors related to liver development.
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