scholarly journals Role of gp91phoxHomolog Nox1 in Induction of Premalignant Spindle Phenotypes of HPV 16 E6/E7—Immortalized Human Keratinocytes

2010 ◽  
Vol 10 ◽  
pp. 1435-1449 ◽  
Author(s):  
Walee Chamulitrat

The NADPH oxidase (Nox) family of superoxide- and hydrogen peroxide—producing proteins has been recognized as important for signal transduction that regulates receptor-mediated functions, including cytoskeleton remodeling, cell proliferation, migration, differentiation, and cell death. Nox1 was the first of the Nox catalytic subunits to be cloned and shown to induce tumorigenic conversion of mouse fibroblasts. While Nox1 has been shown to be expressed in human colon and prostate cancers, however, limited studies have demonstrated the involvement of Nox1 in an early step of cell transformation. The aim of this review is to provide an overview on the role of Nox1 in cancer, as well as the contribution of our studies to demonstrate the involvement of Nox1 on neoplastic progression of human keratinocytes beyond the immortalization step. The generation of spindle phenotypes concomitant with anchorage-independent growth and invasiveness will be highlighted and discussed in relation to the possible role of Nox1 in epithelial-mesenchymal transition. Understanding these mechanisms may provide insight into Nox1 and redox signaling components as potential therapeutic targets to inhibit tumor progression.

Author(s):  
Pedro Carriere ◽  
Natalia Calvo ◽  
María Belén Novoa ◽  
Fernanda Lopez-Moncada ◽  
Alexander Riquelme ◽  
...  

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 414-414
Author(s):  
C. Grandclement ◽  
R. Bedel ◽  
B. Kantelip ◽  
E. Viel ◽  
J. Remy Martin ◽  
...  

414 Background: Initially characterized as neuronal receptors, Neuropilins (NRPs) were also found to be expressed in endothelial cells and subsequently were shown to play a role in the development of the vascular system. NRP family consists of two genes, neuropilin-1 (NRP1) and neuropilin-2 (NRP2).The multiple functions of NRPs were recently highlighted by the identification of NRP role in oncogenesis. In this study, we first confirmed the role of NRP2 in tumor progression. We also extended the understanding of NRP2 oncogenic functions by investigating the ability of NRP2 to orchestrate epithelial-mesenchymal transition (EMT) in colorectal cancer cells. Methods: We have generated human colon cancer cell lines transfected with NRP2 transgene or siRNA to investigate NRP2 involvement in EMT. First, the oncogenic functions of NRP2 were studied in vitro by MTT, soft agar, invasion assays and in vivo using xenografts experiments. Ability of NRP2 to orchestrate EMT was then investigated by flow cytometry, immunohistochemical (IHC) staining, western-blotting and quantitative real-time PCR. Results: IHC staining revealed that NRP2 is expressed in human colon and breast carcinomas while it is not expressed in healthy tissues. Then, we confirmed that NRP2 increases tumor proliferation, colony formation, invasion and xenograft formation. Moreover, NRP2-expressing cells displayed an immunohistochemical phenotype of EMT characterized by the loss of E-Cadherin and an increase of vimentin. Furthermore, NRP2 expression promotes transforming-growth factor-β1 (TGF- β1) signaling, leading to an increased phosphorylation of the Smad2/3 complex in colorectal cancer cell lines. Specific inhibition of NRP2 using siRNA or treatment with specific TGFβRI kinase inhibitors prevented this phosphorylation and the EMT, suggesting that NRP2 cooperates with TGFRI to promote EMT in colorectal carcinoma. Conclusions: Our findings have reinforced the essential role of NRP2 in cancer progression and demonstrated that NRP2 expression confers to tumor cell lines the hallmarks of EMT. Moreover, in the current work, we present evidence for the therapeutic value of NRP2 targeting. No significant financial relationships to disclose.


2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.


2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.


2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Lina A. Aeshra ◽  
Maiada Moustafa ◽  
Mohammed I. Y. Elmallah ◽  
Said Abdelrahman Salih ◽  
Ibrahim Y. Abdel Kader

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhenming Jiang ◽  
Yuxi Zhang ◽  
Xi Chen ◽  
Pingeng Wu ◽  
Dong Chen

An amendment to this paper has been published and can be accessed via the original article.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiabin Yu ◽  
Li Yang ◽  
Hongting Lu

AbstractMalignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.


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