ArticleInternational journal of cancer2017
BOK displays cell death-independent tumor suppressor activity in non-small-cell lung carcinoma.
Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 28 citations in OpenAlex.
- Loss of BOK increases vulnerability of p53 deficient non-small cell lung cancer cells to ATR inhibition through its role in uridine metabolism.Cell death and differentiation · 2026Article
- BOK beyond apoptosis: pyrimidine metabolism and ATR dependence in p53-deficient lung cancer.Cell death and differentiation · 2026Article
- Dual targeting of BCL-XL and MCL-1 exposes a rapid and exploitable apoptotic vulnerability in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Disruption of MCL1/BOK transmembrane interaction as a novel strategy to induce cell death in tumours.Cell death & disease · 2026Article
- Low Expression of a Circular Transcript of the Apoptosis Regulator GeneBiomedicines · 2026Article
- Low BOK Expression Promotes Epithelial-Mesenchymal Transition and Migration via the Wnt Signaling Pathway in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Article
- The Role of BCL-2 and PD-1/PD-L1 Pathway in Pathogenesis of Myelodysplastic Syndromes.International journal of molecular sciences · 2023Review
- Bok: real killer or bystander with non-apoptotic roles?Frontiers in cell and developmental biology · 2023Review
- Garlic Extract Participates in the Proliferation and Apoptosis of Nonsmall Cell Lung Cancer Cells Via Endoplasmic Reticulum Stress Pathway.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner.Oncogene · 2022Article
- Endogenous Bok is stable at the endoplasmic reticulum membrane and does not mediate proteasome inhibitor-induced apoptosis.Frontiers in cell and developmental biology · 2022Article
- Development and Validation of a Novel Survival Model for Cutaneous Melanoma Based on Necroptosis-Related Genes.Frontiers in oncology · 2022Article
- Circ-PGC increases the expression of FOXR2 by targeting miR-532-3p to promote the development of non-small cell lung cancer.Cell cycle (Georgetown, Tex.) · 2021Article
- Long non‑coding RNA SNHG3 promotes the development of non‑small cell lung cancer via the miR‑1343‑3p/NFIX pathway.International journal of molecular medicine · 2021Article
- Balancing ER-Mitochondrial CaTrends in cell biology · 2021Review
- Loss of BOK Has a Minor Impact on Acetaminophen Overdose-Induced Liver Damage in Mice.International journal of molecular sciences · 2021Article
- Balanced Functional Module Detection in genomic data.Bioinformatics advances · 2021Article
- BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy.Apoptosis : an international journal on programmed cell death · 2020Review
- SKA1/2/3 serves as a biomarker for poor prognosis in human lung adenocarcinoma.Translational lung cancer research · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
As the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small-cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (p < 0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (p = 0.004, n = 35) and three (p = 0.031, n = 39) as well as in tumors with metastases to hilar (pN1) (p = 0.047, n = 31) and mediastinal/subcarinal lymph nodes (pN2) (p = 0.021, n = 18) as opposed to grade one tumors (p = 0.688, n = 7) and tumors without lymph node metastases (p = 0.112, n = 51). Importantly, in lymph node-positive patients, BOK expression greater than the median value was associated with longer survival (p = 0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients.
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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.