Expression and mutational analysis of TGF-β/Smads signaling in human cervical cancers

Ki, Kyung‐Do; Tong, Seo Yun; Huh, Chu Yeop; Lee, Jong Min; Lee, Seon Kyung; Gil, Sung

doi:10.3802/jgo.2009.20.2.117

Cited by 23 publications

(14 citation statements)

References 17 publications

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“…In recent years, a large number of studies demonstrated that TGF-β1 is an important cytokine in airway remodeling (20–22). Smads are the group of intracellular proteins that are critical for transmitting the TGF-β1 signals from the cell surface to the nucleus to promote transcription of target genes (23,24). In our study, we investigated the expression of active TGF-β1 signaling by detecting the expression of the intracellular effectors, Smads.…”

Section: Discussionmentioning

confidence: 99%

Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice

Yang²,

Chen³

et al. 2011

International Journal of Molecular Medicine

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Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and increased mucous glands, which can lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we investigated whether the astragalus extract inhibits airway remodeling in a mouse asthma model and observed the effects of astragalus extract on the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in ovalbumin-sensitized mice. Mice were sensitized and challenged by ovalbumin to establish a model of asthma. Treatments included the astragalus extract and budesonide. Lung tissues were obtained for hematoxylin and eosin staining and Periodic acid-Schiff staining after the final ovalbumin challenge. Levels of TGF-β1 were assessed by immunohistology and ELISA, levels of TGF-β1 mRNA were measured by RT-PCR, and levels of P-Smad2/3 and T-Smad2/3 were assessed by western blotting. Astragalus extract and budesonide reduced allergen-induced increases in the thickness of bronchial airway and mucous gland hypertrophy, goblet cell hyperplasia and collagen deposition. Levels of lung TGF-β1, TGF-β1 mRNA and P-Smad2/3 were significantly reduced in mice treated with astragalus extract and budesonide. Astragalus extract improved asthma airway remodeling by inhibiting the expression of the TGF-β1/Smad signaling pathway, and may be a potential drug for the treatment of patients with a severe asthma airway.

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Section: Discussionmentioning

confidence: 99%

Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice

Yang²,

Chen³

et al. 2011

International Journal of Molecular Medicine

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“…52 However, a prominent aspect of malignant transformation in cervical epithelial cells is the progressive loss of TGF-β responsiveness. 53 In this respect, studies demonstrate a contributing role for HPV in the acquisition of TGF-β nuclear translocation, which may play a crucial role in the HPV-induced cervical carcinogenesis. 55 Through decreasing the intracellular levels of TIP-2/GIPC, a PDZ protein involved in the expression of TGFbRIII, HPV18 E6 was shown to render HeLa cells less sensitive to the antigrowth activities of TGF-β.…”

Section: Human Papilloma Virusmentioning

confidence: 99%

Viruses as key modulators of the TGF‐β pathway; a double‐edged sword involved in cancer

Mirzaei

Faghihloo

2018

Reviews in Medical Virology

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Transforming growth factor-β (TGF-β) signaling pathway is a key network in cell signaling that controls vital processes such as proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and migration, thus acting as a double-edged sword in normal development and diseases, in particular organ fibrosis, vascular disorders, and cancer. Early in tumorigenesis, the pathway exerts anti-tumor effects through suppressing cell cycle and inducing apoptosis, while during late stages, it functions as a tumor promoter by enhancing tumor invasiveness and metastasis. This signaling pathway can be perturbed by environmental and genetic factors such as microbial interference and mutation, respectively. In this way, the present review describes the modulation of the TGF-β pathway by oncogenic human viral pathogens and other viruses. The main mechanisms by which viruses interferes with TGF-β signaling seems to be through (1) the alteration of either TGF-β protein expression or activation, (2) the modulation of the TGF-β receptors or SMADs factors (by interfering with their levels and functions), (3) the alteration of none-SMAD pathways, and (4) indirect interaction with the pathway by the modulation of transcriptional co-activator/repressor and regulators of the pathway. Given the axial role of this pathway in tumorigenesis, it can be regarded as an attractive target for cancer therapy. Hence, further investigations on this subject may represent molecular targets among either TGF-β signaling molecules or viral factors for the treatment and management of viral infection consequences such as cancer.

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“…62 Alterations of the TGF-b/Smad signalling pathway, which is tightly regulated by E3 ubiquitin ligases, 63 are related to a range of human cancers, including cervical carcinoma. 64 FavreBonvin et al 65 reported that HPV18 E6 protein interacts with a protein containing the PDZ domain, TIP-2/GIPC (Tax interacting protein, clone 2/GAIP interacting protein, C terminus) (Table 1), triggering its degradation through the ubiquitin-proteasome pathway. As this PDZ protein has been found to be involved in TGF-b signalling by favouring expression of the TGF-b type III receptor at the cell membrane, the depletion of TIP-2/GIPC in HeLa cells hampers TGF-b signalling and also diminishes the antiproliferative effect of TGF-b.…”

Section: E3 Ubiquitin Ligases In Tgf-/smad Signallingmentioning

confidence: 99%

E3 ubiquitin ligases and human papillomavirus-induced carcinogenesis

Lou

Wang²

2014

J Int Med Res

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Human papillomavirus (HPV) infection is clinically very common. It is usually a major risk factor in the development of cutaneous benign lesions, cervical cancer and a variety of other malignancies. The biological function of ubiquitination as an intracellular proteasomal-mediated form of protein degradation and an important modulator in the regulation of many fundamental cellular processes has been increasingly recognized over the last decade. HPV proteins have been demonstrated to evolve different strategies to utilize the ubiquitin system for their own purposes. The putative roles of E3 ubiquitin ligases in HPV-induced carcinogenesis have become increasingly apparent, although the mechanisms remain unclear. In this review we provide an update on the mechanisms of the involvement of E3 ubiquitin ligases in HPV-induced carcinogenesis, focusing on their interaction with HPV proteins and their roles in several signalling pathways. Targeting the E3 ubiquitin ligases might offer potential therapeutic strategies for HPV-related diseases in future.

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Expression and mutational analysis of TGF-β/Smads signaling in human cervical cancers

Cited by 23 publications

References 17 publications

Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice

Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice

Viruses as key modulators of the TGF‐β pathway; a double‐edged sword involved in cancer

E3 ubiquitin ligases and human papillomavirus-induced carcinogenesis

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