ArticleJournal of Cancer2015
The Expression and Function of NUMB in Endometrial Cancer and the Interaction with HDM2 and P53.
Article in Journal of Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Expression of NUMB Protein and Its Prognostic Significance in Endometrial Cancer: A Retrospective Cohort Study.Cureus · 2025Article
- Review
- Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool.The Journal of cell biology · 2022Article
- NUMB suppression by miR-9-5P enhances CD44Scientific reports · 2021Article
- miR-335 modulates Numb alternative splicing via targeting RBM10 in endometrial cancer.The Kaohsiung journal of medical sciences · 2020Article
- Numb inhibits cell proliferation, invasion, and epithelial-mesenchymal transition through PAK1/β-catenin signaling pathway in ovarian cancer.OncoTargets and therapy · 2019Article
- [Advances in research on cell fate determinant Numb regulating liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2018Review
- Inhibition on Numb/Notch signal pathway enhances radiosensitivity of lung cancer cell line H358.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSince more and more evidences support that NUMB orchestrates many cell physiological and pathological processes of diseases including cancer, based on our previous work, we studied deeply the function of NUMB in endometrial cancer (EC) and tried to understand the mechanism of NUMB's nucleus translocation which might be relative to the occurrence of EC and will contribute to find a new targeting therapeutic strategy for EC.
methodsImmunohistochemistry was employed to test NUMB and HDM2 expression in endometrial cancer tissue from clinical patients. CCK-8 assay, cell cycle tested by Flow cytometer and PCNA determined by RT-PCR were employed to test the effects of NUMB on cell proliferation and apoptosis. In order to investigate the mechanism how NUMB, HDM2 and p53 interact in EC cell, western blot, Co-IP and immunofluorescent were used to observe the combination and location of NUMB, HDM2 and p53 as well as the interaction among them.
resultsBoth NUMB and HDM2 expressed greater in endometrial cancer tissues than in normal endometrial tissues. Overexpression of NUMB induced apoptosis in Ishikawa cell while inhibition of NUMB increased cell proliferation. NUMB could combine HDM2 and p53, moreover the PTB domain of NUMB is the main site combining with p53. The effects of NUMB in cell was closely associated with p53. Not only NUMB regulated P53 expression level but also NUMB acts depending on P53, in turn p53 impacted the NUMB level as a feedback. Overexpression of NUMB could not bring itself into nuclear. Both siHDM2 and siP53 didn't bring NUMB into nucleus, However overexpression of HDM2 and p53 increased the NUMB level in nucleus, and the NUMB nuclear location induced by overexpression of HDM2 was stronger than that of p53 overexpression.
conclusionsBased on present data, we think NUMB acts as an anti-oncogene role and could regulate p53 level and function in endometrial cancer like in other cancers, meanwhile, the function of NUMB depend on P53. On the other hand, the location of NUMB could be regulated mainly by HDM2. So far we are not able to explain why endometrial cancer patients had high NUMB expression level since NUMB was regarded as a tumor suppressor, which is worthy studying further to explore underlying mechanism.
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