ArticleOncogene2005
17beta-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- Mitochondrial Function Under Combined Oral Contraceptive Exposure in a Neuroblastoma Model: A Preliminary Investigation.Biomedicines · 2026Article
- WWOX Induction Promotes Bcl-XCells · 2026Article
- Review
- Dissociation of the nuclear WWOX/TRAF2 switch renders UV/cold shock-mediated nuclear bubbling cell death at low temperatures.Cell communication and signaling : CCS · 2024Article
- Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration.International journal of molecular sciences · 2024Review
- Loss of fragile WWOX gene leads to senescence escape and genome instability.Cellular and molecular life sciences : CMLS · 2023Article
- WWOX and metabolic regulation in normal and pathological conditions.Journal of molecular medicine (Berlin, Germany) · 2022Review
- TGFα-EGFR pathway in breast carcinogenesis, association with WWOX expression and estrogen activation.Journal of applied genetics · 2022Article
- Review
- Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299.Communications biology · 2021Article
- Cellular Expression and Subcellular Localization of Wwox Protein During Testicular Development and Spermatogenesis in Rats.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Article
- Article
- TheExperimental biology and medicine (Maywood, N.J.) · 2020Review
- Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression.Bioscience reports · 2020Observational
- Article
- WWOX PossessesCancers · 2019Article
- A p53/TIAF1/WWOX triad exerts cancer suppression but may cause brain protein aggregation due to p53/WWOX functional antagonism.Cell communication and signaling : CCS · 2019Article
- Ectopic expression of HSDL2 is related to cell proliferation and prognosis in breast cancer.Cancer management and research · 2019Article
- Strategies by which WWOX-deficient metastatic cancer cells utilize to survive via dodging, compromising, and causing damage to WWOX-positive normal microenvironment.Cell death discovery · 2019Article
- Somatic loss of WWOX is associated with TP53 perturbation in basal-like breast cancer.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human WWOX gene encodes a proapoptotic WW domain-containing oxidoreductase WOX1 (also named WWOX, FOR2 or WWOXv1). Apoptotic and stress stimuli activate WOX1 via Tyr33 phosphorylation and nuclear translocation. WOX1 possesses a tetrad NSYK motif in the C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, which may bind estrogen and androgen. Here, we determined that 17beta-estradiol (E(2)) activated WOX1, p53 and ERK in COS7 fibroblasts, primary lung epithelial cells, and androgen receptor (AR)-negative prostate DU145 cells, but not in estrogen receptor (ER)-positive breast MCF7 cells. Androgen also activated WOX1 in the AR-negative DU145 cells. These observations suggest that sex hormone-mediated Tyr33 phosphorylation and nuclear translocation of WOX1 is independent of ER and AR. Stress stimuli increase physical binding of p53 with WOX1 in vivo. We determined here that E(2) increased the formation of p53/WOX1 complex and their nuclear translocation in COS7 cells; however, nuclear translocation of this complex could not occur in MCF7 cells. By immunohistochemistry, we determined that progression of prostate from normal to hyperplasia, cancerous and metastatic stages positively correlate with upregulation and activation of WOX1 and WOX2 (FOR1/WWOXv2). In contrast, breast cancer development to a premetastatic state is associated with upregulation and Tyr33 phosphorylation of cytosolic WOX1 and WOX2, followed by significant downregulation or absent expression during metastasis. These Tyr33-phosphorylated proteins are mostly located in the mitochondria without translocating to the nuclei, which is comparable to those findings in cultured breast cancer cells. Together, sex steroid hormone-induced activation of WOX1 and WOX2 is independent of ER and AR, and this activation positively correlates with cancerous progression of prostate and breast to a premetastatic state.
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