ArticleThe Journal of clinical investigation2022
FOXK2 promotes ovarian cancer stemness by regulating the unfolded protein response pathway.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- pCancer and FOXK2 (Forkhead Box K2): Oncogenic and Tumor-Suppressive Roles of FOXK2 in Cancer.Biochemical genetics · 2026Review
- HMGB1-mediated endoplasmic reticulum stress in monocyte-derived dendritic cells regulates CD4+ T cell immune responses in myasthenia gravis.Journal of neuroinflammation · 2026Article
- Targeting cancer stem cells predicts response and reverses chemoresistance in ascites-derived ovarian cancer organoids.BMC medicine · 2026Article
- Article
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- KIRA6 restrains the generation of myeloid-derived suppressor cells and overcomes resistance to anti-PD-1 therapy.Cell death & disease · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- FOXK2 amplification promotes breast cancer development and chemoresistance.Cancer letters · 2024Article
- Phosphorylation of FOXK2 at Thr13 and Ser30 by PDK2 sustains glycolysis through a positive feedback manner in ovarian cancer.Oncogene · 2024Article
- NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells.Journal of ovarian research · 2024Article
- Nanoparticle Targeting in Chemo-Resistant Ovarian Cancer Reveals Dual Axis of Therapeutic Vulnerability Involving Cholesterol Uptake and Cell Redox Balance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploiting the Warburg Effect: Co-Delivery of Metformin and FOXK2 siRNA for Ovarian Cancer Therapy.Small science · 2024Article
- Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.Cell communication and signaling : CCS · 2024Review
- Endoplasmic reticulum stress response pathway-mediated cell death in ovarian cancer.Frontiers in oncology · 2024Review
- Emerging roles of FOXK2 in cancers and metabolic disorders.Frontiers in oncology · 2024Review
- TRIM Expression in HNSCC: Exploring the Link Between Ubiquitination, Immune Infiltration, and Signaling Pathways Through Bioinformatics.International journal of general medicine · 2024Article
- Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Understanding the regulatory programs enabling cancer stem cells (CSCs) to self-renew and drive tumorigenicity could identify new treatments. Through comparative chromatin-state and gene expression analyses in ovarian CSCs versus non-CSCs, we identified FOXK2 as a highly expressed stemness-specific transcription factor in ovarian cancer. Its genetic depletion diminished stemness features and reduced tumor initiation capacity. Our mechanistic studies highlight that FOXK2 directly regulated IRE1α (encoded by ERN1) expression, a key sensor for the unfolded protein response (UPR). Chromatin immunoprecipitation and sequencing revealed that FOXK2 bound to an intronic regulatory element of ERN1. Blocking FOXK2 from binding to this enhancer by using a catalytically inactive CRISPR/Cas9 (dCas9) diminished IRE1α transcription. At the molecular level, FOXK2-driven upregulation of IRE1α led to alternative XBP1 splicing and activation of stemness pathways, while genetic or pharmacological blockade of this sensor of the UPR inhibited ovarian CSCs. Collectively, these data establish what we believe is a new function for FOXK2 as a key transcriptional regulator of CSCs and a mediator of the UPR, providing insight into potentially targetable new pathways in CSCs.
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Registered trials
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.