Control of transforming growth factor β signal transduction by small GTPases

Kardassis, Dimitris; Murphy, Carol; Fotsis, Theodore; Moustakas, Aristidis; Stournaras, Christos

doi:10.1111/j.1742-4658.2009.07031.x

Cited by 94 publications

(91 citation statements)

References 163 publications

(226 reference statements)

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“…Bioinformatic analysis demonstrated a slight annotation enrichment of proteins involved in ECM-receptor interaction (Table IV), regulation of actin cytoskeleton, the spliceosome (Table V), DNA replication (Table VI), adherens or tight junctions and focal adhesion, which are established signaling responses to TGF-β (10,(66)(67)(68). Proteins in these signaling pathways may be potential markers of metastasis and targets for glioblastoma treatment.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Bryukhovetskiy

Шевченко

2016

Oncology Letters

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Abstract. Glioblastoma multiforme (GBM) is the most widespread and aggressive type of primary brain tumor. The prognosis following diagnosis with GBM is poor, with a median survival time of 14 months. Tumor cell invasion, metastasis and proliferation are the major causes of mortality in patients with GBM. In order to develop effective GBM treatment methods it is necessary to identify novel targets involved in these processes. Recently, there has been increasing interest in investigating the signaling pathways involved in GBM development, and the transforming growth factor-β (TGF-β) signaling pathway is understood to be significant for regulating the behavior of GBM, as well as stimulating its invasion and metastatic development. Particular interest has been given to investigating the modulation of TGF-β-induced epithelial-to-mesenchymal transition (EMT); during this process, epithelial cells transdifferentiate into mobile cells with a mesenchymal phenotype. The induction of EMT increases the invasiveness of various types of carcinoma; however, the role of TGF-β in this process remains to be elucidated, particularly in the case of GBM. The current study presents a comparative proteome mapping of the U87 human glioblastoma cell line, with and without TGF-β1 treatment. Proteome analysis identified numerous proteins involved in the molecular mechanisms of GBM oncogenesis and TGF-β1 signaling in glioblastoma. The results of the present study facilitated the identification of novel potential markers of metastasis and candidates for targeted glioblastoma therapy, which may potentially be validated and used in clinical medicine to develop improved approaches for GBM diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Bryukhovetskiy

Шевченко

2016

Oncology Letters

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“…In different tissues (Kardassis et al 2009), including prostate (Fibbi et al 2010), an interplay of TGFb and RhoA/ROCK signaling have been recognized at the crossroads of inflammatory response and fibrosis. Consistent with this view, expression of TGFb and RhoA/ROCK is upregulated in HFD prostate.…”

Section: Discussionmentioning

confidence: 99%

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit

Vignozzi¹,

Morelli²,

Sarchielli³

et al. 2011

Journal of Endocrinology

172

174

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Metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) are often associated. One of their common denominators is hypogonadism. However, testosterone supplementation is limited by concerns for potential prostatic side effects. The objective was to determine whether MetS-associated prostate alterations are prevented by testosterone supplementation. We used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks. Subsets of HFD rabbits were treated with testosterone or with the farnesoid X receptor agonist INT-747. Rabbits fed a standard diet were used as controls. HFD-animals develop hypogonadism and all the MetS features: hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. In addition, HFD-animals show a prostate inflammation. Immunohistochemical analysis demonstrated that HFD-induced prostate fibrosis, hypoxia, and inflammation.The mRNA expression of several proinflammatory (IL8, IL6, IL1b, and TNFa), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR gt), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGFb, SM22a, aSMA, RhoA, and ROCK1/ROCK2) markers was significantly increased in HFD prostate. Testosterone, as well as INT-747, treatment prevented some MetS features, although only testosterone normalized all the HFD-induced prostate alterations. Interestingly, the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and the majority of inflammatory markers analyzed. These data highlight that testosterone protects rabbit prostate from MetS-induced prostatic hypoxia, fibrosis, and inflammation, which can play a role toward the development/progression of BPH/LUTS.

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“…Among these small G proteins, the Ras subfamily is the most studied for its critical roles in human oncogenesis (Cheng et al, 2005). RAB proteins have been reported to have vital roles in vesicle trafficking, signal transduction and receptor recycling, which in turn regulate normal cellular activity (Rosenfeld et al, 2002;Kardassis et al, 2009). Therefore, RAB dysfunction might be involved in human cancers and other diseases.…”

Section: Microrna-451 Functions As a Tumor Suppressor In Human Nsclcmentioning

confidence: 99%

MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14)

et al. 2011

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Accumulating evidence suggests that microRNAs (miRNAs) are important gene regulators, which can have critical roles in diverse biological processes including tumorigenesis. In this study, we analyzed the miRNA expression profiles in non-small cell lung carcinoma (NSCLC) by use of a miRNA microarray platform and identified 40 differentially expressed miRNAs. We showed that miRNA (miR)-451 was the most downregulated in NSCLC tissues. The expression level of miR-451 was found to be significantly correlated with tumor differentiation, pathological stage and lymph-node metastasis. Moreover, low miR-451 expression level was also correlated with shorter overall survival of NSCLC patients (Po0.001). Ectopic miR-451 expression significantly suppressed the in vitro proliferation and colony formation of NSCLC cells and the development of tumors in nude mice by enhancing apoptosis, which might be associated with inactivation of Akt signaling pathway. Interestingly, ectopic miR-451 expression could significantly inhibit RAB14 protein expression and decrease a luciferasereporter activity containing the RAB14 3 0 -untranslated region (UTR). In addition,, RNA interference silencing of RAB14 gene could recapitulate the tumor suppressor function of miR-451, whereas restoration of RAB14 expression could partially attenuate the tumor suppressor function of miR-451 in NSCLC cells. Furthermore, we also showed that strong positive immunoreactivity of RAB14 protein was significantly associated with downregulation of miR-451 (P ¼ 0.01). These findings suggest that miR-451 regulates survival of NSCLC cells partially through the downregulation of RAB14. Therefore, targeting with the miR-451/RAB14 interaction might serve as a novel therapeutic application to treat NSCLC patients.

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Control of transforming growth factor β signal transduction by small GTPases

Cited by 94 publications

References 163 publications

Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit

MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14)

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