ArticleOncogene2022
Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance in a FGF7-FGFR2 autocrine pathway.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- SOX9 promotes hepatocyte proliferation via upregulating TGF-α expression during liver regeneration.Hepatology international · 2026Article
- N6-methyladenosine-mediated up-regulation of ARRB2 regulates intrahepatic cholangiocarcinoma malignant progression and pemigatinib resistance through MAPK and Hippo signaling pathways.Cell death & disease · 2026Article
- FGF7-FGFR2 Signaling Enhances Contractile Activation of CAFs in Ovarian Cancer: Integrative Single-Cell and Spatial Transcriptomics.Journal of inflammation research · 2026Article
- FGF1-FGFR2 axis regulated by nuclear receptor RORγ represents an effective strategy in intrahepatic cholangiocarcinoma.Cell death discovery · 2025Article
- Targeting the ROCK2/UBA52/DRP1 axis enhances ferroptosis and overcomes pemigatinib resistance in Cholangiocarcinoma.Cell death & disease · 2025Article
- TCF7 enhances pulmonary hypertension by boosting stressed natural killer cells and their interaction with pulmonary arterial smooth muscle cells.Respiratory research · 2025Article
- Bile-Derived cfDNA of Syncytin-1 and SLC7A11 as a Potential Molecular Marker for Early Diagnosis of Cholangiocarcinoma.Journal of gastrointestinal cancer · 2025Article
- SOX9: a novel janus-faced regulator in immunity and its promise as a therapeutic target.Frontiers in molecular biosciences · 2025Review
- Function of histamine-driven cancer-associated fibroblast and hepatocyte growth factor in the progression of cholangiocarcinoma.Gastroenterology report · 2025Article
- Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance.Biomolecules · 2024Review
- Super-Enhancer Reprograming Driven by SOX9 and TCF7L2 Represents Transcription-Targeted Therapeutic Vulnerability for Treating Gallbladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A-to-I-edited miR-1251-5p restrains tumor growth and metastasis in lung adenocarcinoma through regulating TCF7-mediated Wnt signaling pathway.Discover oncology · 2024Article
- Personalized treatment of perihilar cholangiocarcinoma based on tumor genetic and molecular characteristics.World journal of gastrointestinal surgery · 2024Article
- Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics.Protein & cell · 2024Article
- Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter.Journal of translational medicine · 2024Article
- TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma.EMBO reports · 2024Article
- Protocol of REACH-01: a single-arm, open label, prospective study of HAIC sequential TAE combined with tislelizumab and surufatinib in unresectable intrahepatic cholangiocarcinoma.Frontiers in pharmacology · 2024Article
- A spatiotemporal gene expression and cell atlases of the developing rat ovary.Cell proliferation · 2023Article
- SOX18 Promotes the Proliferation of Dermal Papilla Cells via the Wnt/β-Catenin Signaling Pathway.International journal of molecular sciences · 2023Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocarcinoma (CCA) is a type of highly malignant tumor originating from bile ducts. The prognosis of CCA is poor and the treatment options are limited. The biomarker study of CCA has made little progresses in recent years because of the difficulty to obtain CCA specimens. SOX9 is an important regulator of cholangiocyte proliferation and differentiation. We performed mRNA sequencing of CCA, retrieved TCGA data, and detected SOX9 expression in a large CCA cohort. With WNT3A stimulation, SOX9 expression and transcription was elevated by TCF7. Moreover, SOX9 was substantially up-regulated in CCA tissues and was identified as a prognostic biomarker of CCA. With mRNA sequencing and in vitro/vivo validation, we demonstrated that SOX9 enhanced the transcription and expression of FGF7 and FGFR2. FGF7 was significantly up-regulated in the bile and serum of CCA patients, and may promote CCA proliferation by activating FGFR2 in an autocrine pathway. co-expression of FGF7 and FGFR2 was a more sensitive marker for poor prognosis. SOX9-induced overexpression of FGF7 and FGFR2 was the key reason of SOX9-involved pemigatinib resistance. In conclusion, SOX9 and FGF7 were prognostic biomarkers of CCA. WNT3A-TCF7-SOX9 axis could induce pemigatinib resistance in two independent pathways: (1)SOX9 directly promotes FGFR2 transcription and expression; (2)SOX9 elevates FGF7 expression, which could be secreted from CCA cells and activates FGFR2 phosphorylation in an autocrine pathway.
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