ArticleOncogene2021
FOXK2 transcriptionally activating VEGFA induces apatinib resistance in anaplastic thyroid cancer through VEGFA/VEGFR1 pathway.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- FOXK2/SH2D3A axis recruits EGFR to drive papillary thyroid cancer progression and confers sensitivity to EGFR inhibition.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- Tumor microenvironment-guided targeted and immunotherapy in anaplastic thyroid cancer: a literature review from preclinical models to clinical translation.Translational cancer research · 2026Review
- Post-translational modifications in anaplastic thyroid carcinoma: biological mechanisms and therapeutic potential.Cancer cell international · 2025Review
- The endoplasmic reticulum stress-ferroptosis reciprocal signaling orchestrates anti-tumor effect of anlotinib in anaplastic thyroid cancer.Cancer cell international · 2025Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- The role of FOXK2-FBXO32 in breast cancer tumorigenesis: Insights into ribosome-associated pathways.Thoracic cancer · 2025Article
- Enhancing antitumor immunity: the role of immune checkpoint inhibitors, anti-angiogenic therapy, and macrophage reprogramming.Frontiers in oncology · 2025Review
- SLC7A9 suppression increases chemosensitivity by inducing ferroptosis via the inhibition of cystine transport in gastric cancer.EBioMedicine · 2024Article
- Combined detection of inflammatory proteins is beneficial for diagnosing the papillary thyroid carcinoma and nodular goiter.iMetaOmics · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Study on the mechanism of heterogeneous tumor-associated macrophages in three subtypes of breast cancer through the integration of single-cell RNA sequencing and in vitro experiments.Molecular biology reports · 2024Article
- HOXD3 promotes the migration and angiogenesis of hepatocellular carcinoma via modifying hepatocellular carcinoma cells exosome-delivered CCR6 and regulating chromatin conformation of CCL20.Cell death & disease · 2024Article
- Atlas of cardiac endothelial cell enhancer elements linking the mineralocorticoid receptor to pathological gene expression.Science advances · 2024Article
- Genome-wide CRISPR screen identifies ESPL1 limits the response of gastric cancer cells to apatinib.Cancer cell international · 2024Article
- Autophagic blockade potentiates anlotinib-mediated ferroptosis in anaplastic thyroid cancer.Endocrine-related cancer · 2023Article
- Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy.Journal of experimental & clinical cancer research : CR · 2023Article
- HSPA5 Promotes the Proliferation, Metastasis and Regulates Ferroptosis of Bladder Cancer.International journal of molecular sciences · 2023Article
- Case report: Apatinib combined with neoadjuvant therapy for primary squamous cell carcinoma of the breast: a case report.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anaplastic thyroid carcinoma (ATC) is a rare and extremely aggressive type of thyroid cancer, and the potential mechanisms involved in ATC progression remains unclarified. In this study, we found that forkhead box K2 (FOXK2) was upregulated in ATC tissues, and the expression of FOXK2 was associated with tumor size. Evidenced by RNA-seq and Chromatin immunoprecipitation (ChIP)-seq assays, FOXK2 positively regulated VEGF and VEGFR signaling network, among which only VEGFA could be noticed in both RNA-seq and ChIP-seq results. ChIP, dual-luciferase reporter system and functional experiments further confirmed that FOXK2 promoted angiogenesis by inducing the transcription of VEGFA. On VEGFR2 blockage by specific targeting agent, such as Apatinib, FOXK2 could rapidly trigger therapeutic resistance. Mechanical analyses revealed that VEGFA transcriptionally induced by FOXK2 could bind to VEGFR1 as a compensation for VEGFR2 blockage, which promoted angiogenesis by activating ERK, PI3K/AKT and P38/MAPK signaling in human umbilical vein endothelial cells (HUVECs). Synergic effect on anti-angiogenesis could be observed when VEGFR1 suppressor AF321 was included in VEGFR2 inhibition system, which clarified the pivot role of FOXK2 in VEGFR2 targeting therapy resistance. More importantly, the binding of VEGFA to VEGFR1 could further promoter FOXK2-mediated VEGFA transcription, which consequently constituted a positive feedback loop. Therefore, the novel loop VEGFA/VEGFR1/FOXK2 functioned importantly in resistance to VEGFR2 targeting therapy in FOXK2
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