ArticleBMC cancer2013
Partial loss of Smad signaling during in vitro progression of HPV16-immortalized human keratinocytes.
Article in BMC cancer, 2013. 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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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
8 citing papers in PubMed, 27 citations in OpenAlex.
- Disease-linked regulatory DNA variants and homeostatic transcription factors in epidermis.Nature communications · 2025Article
- Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-β signaling responses in ovarian cancer.Cell communication and signaling : CCS · 2024Article
- ESRRB Inhibits the TGFβ Signaling Pathway to Drive Cell Proliferation in Cervical Cancer.Cancer research · 2023Article
- Stem Cell Properties of Normal Human Keratinocytes Determine Transformation Responses to Human Papillomavirus 16 DNA.Journal of virology · 2018Article
- In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment.Oncotarget · 2016Article
- MiR-519d facilitates the progression and metastasis of cervical cancer through direct targeting Smad7.Cancer cell international · 2016Article
- Article
- The translational significance of epithelial-mesenchymal transition in head and neck cancer.Clinical and translational medicine · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDisruption of the transforming growth factor-beta (TGF-β) signaling pathway is observed in many cancers, including cervical cancer, resulting in TGF-β resistance. While normal human keratinocytes (HKc) and human papillomavirus type 16-immortalized HKc (HKc/HPV16) are sensitive to the growth inhibitory effects of TGF-β, HKc/HPV16 develop resistance to TGF-β1 as they progress in vitro to a differentiation resistant phenotype (HKc/DR). The loss of sensitivity to the antiproliferative effects of TGF-β1 in HKc/DR is due, at least partially, to decreased expression of the TGF-β receptor type I. In the present study, we explored in detail whether alterations in Smad protein levels, Smad phosphorylation, or nuclear localization of Smads in response to TGF-β could contribute to the development of TGF-β resistance during in vitro progression of HKc/HPV16, and whether TGF-β induction of a Smad-responsive reporter gene was altered in HKc/DR.
methodsWestern blot analysis was used to assess Smad protein levels. In order to study Smad nuclear localization we performed indirect immunofluorescence. In addition, we determined Smad-mediated TGF-β signaling using a luciferase reporter construct.
resultsWe did not find a decrease in protein levels of Smad2, Smad3 or Smad4, or an increase in the inhibitory Smad7 that paralleled the loss of sensitivity to the growth inhibitory effects of TGF-β1 observed in HKc/DR. However, we found diminished Smad2 phosphorylation, and delayed nuclear Smad3 localization in response to TGF-β1 in HKc/DR, compared to normal HKc and TGF-β sensitive HKc/HPV16. In addition, we determined that TGF-β1 induction of a Smad responsive promoter is reduced by about 50% in HKc/DR, compared to HKc/HPV16.
conclusionsThese results demonstrate that alterations in Smad protein levels are not associated with the loss of response to the antiproliferative effects of TGF-β in HKc/DR, but that diminished and delayed Smad phosphorylation and nuclear localization, and decreased Smad signaling occur in response to TGF-β in HKc/DR.
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