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Special Issue "Molecular Research of Carcinogenesis"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology".

Deadline for manuscript submissions: closed (30 July 2013)

Special Issue Editor

Guest Editor
Dr. Laurence Huc (Website)

INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France
Interests: proto-oncogenes; tumor suppressor genes; ageing; carcinogens; initiation; promotion; metastasis; oxidative stress; energetic metabolism

Special Issue Information

Dear Colleagues,

Carcinogenesis is a multiparametric process that involves diverse factors such as genetic, environmental or ageing. If data about genetic (proto-oncogenes, tumor suppressors, metastasis suppressors) are quite well-documented, the challenge is now to establish the impact of the environment (chemical, physical, viral) on tumoral progression. Some xenobiotics have deleterious effects on normal cells and then, can initiate cancer transformation and or promote cancer progression. Mutagens, by targeting DNA, have a direct effect on cellular carcinogenesis but many compounds have pleitropic effects, acting on proliferation, apoptosis, cell motility, oxidative stress, energetic metabolism... This special issue will tackle to complex problematic of molecular carcinogenesis and will gather works dealing with the mechanisms involved in chemical, physical and viral carcinogenesis but also ageing-related carcinogenesis and the role of tumour-associated genes.

Dr. Laurence Huc
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF.

Keywords

  • proto-oncogenes
  • tumor suppressor genes
  • ageing
  • carcinogens
  • initiation
  • promotion
  • metastasis
  • oxidative stress
  • energetic metabolism

Published Papers (5 papers)

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Research

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Open AccessArticle Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway
Int. J. Mol. Sci. 2013, 14(10), 20768-20792; doi:10.3390/ijms141020768
Received: 9 July 2013 / Revised: 23 September 2013 / Accepted: 3 October 2013 / Published: 16 October 2013
Cited by 17 | PDF Full-text (1241 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. [...] Read more.
Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. The EMT of hepatocellular carcinoma (HCC) cells is thought to be a key event in intrahepatic dissemination and distal metastasis. In this study, we used 12-O-tet-radecanoylphorbol-13-acetate (TPA) to dissect the signaling pathways involved in the EMT of HepG2 hepatocarcinoma cells. The spectacular change in phenotype induced by TPA, leading to a pronounced spindle-shaped fibroblast-like cell morphology, required ERK1/2 activation. This ERK1/2-dependent EMT process was characterized by a loss of E-cadherin function, modification of the cytoskeleton, the acquisition of mesenchymal markers and profound changes to extracellular matrix composition and mobility. Snail was essential for E-cadherin repression, but was not sufficient for full commitment of the TPA-triggered EMT. We found that TPA triggered the formation of a complex between Snail and β-catenin that activated the Wnt pathway. This study thus provides the first evidence for the existence of a complex network governed by the ERK1/2 signaling pathway, converging on the coregulation of Snail and the Wnt/β-catenin pathway and responsible for the onset and the progression of EMT in hepatocellular carcinoma cells. Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
Open AccessArticle Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer
Int. J. Mol. Sci. 2013, 14(8), 16617-16637; doi:10.3390/ijms140816617
Received: 17 May 2013 / Revised: 19 July 2013 / Accepted: 24 July 2013 / Published: 12 August 2013
Cited by 6 | PDF Full-text (1201 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK) pathway for treatment of these cancers. Many downstream [...] Read more.
Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK) pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β), and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl) or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952) and type II (ARK1) endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth. Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
Open AccessArticle The L10P Polymorphism and Serum Levels of Transforming Growth Factor β1 in Human Breast Cancer
Int. J. Mol. Sci. 2013, 14(8), 15376-15385; doi:10.3390/ijms140815376
Received: 21 June 2013 / Revised: 13 July 2013 / Accepted: 15 July 2013 / Published: 24 July 2013
Cited by 6 | PDF Full-text (773 KB) | HTML Full-text | XML Full-text
Abstract
The L10P single nucleotide polymorphism (SNP) is located in the signal sequence of the transforming growth factor β1 (TGFβ1) gene. The proline-encoding (Pro-) allele of this SNP has been associated with an increased breast cancer risk, which has been attributed [...] Read more.
The L10P single nucleotide polymorphism (SNP) is located in the signal sequence of the transforming growth factor β1 (TGFβ1) gene. The proline-encoding (Pro-) allele of this SNP has been associated with an increased breast cancer risk, which has been attributed to the elevated secretion of this TGFβ1 variant observed in vitro and in male subjects. Here we investigated the association of the L10P SNP with serum levels of TGFβ1 in female breast cancer patients and controls. We genotyped the L10P SNP in 276 breast cancer patients and 255 controls. Serum TGFβ1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of the study population (n = 211). We found no evidence for an association of the L10P SNP with breast cancer risk (per-allele odds ratio: 0.91; 95% confidence interval: 0.71–1.16). However, patients with the Pro/Pro genotype exhibited a significantly younger age at breast cancer onset (55.2 ± 14.3 years) than Leu/Leu patients (60.6 ± 13.6 years; p = 0.04), which may reflect the ability of TGFβ to promote tumor progression. Mean TGFβ1 serum levels of Pro-allele carriers were 39.4 ± 7.4 ng/mL, whereas those of Leu/Leu subjects were 37.6 ± 6.0 ng/mL (p = 0.07). Thus, compared to a previous study of male subjects, we observed only a modest increase, if any, in TGFβ1 levels of female Pro-allele carriers. Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
Open AccessArticle Pilot Study of CYP2B6 Genetic Variation to Explore the Contribution of Nitrosamine Activation to Lung Carcinogenesis
Int. J. Mol. Sci. 2013, 14(4), 8381-8392; doi:10.3390/ijms14048381
Received: 14 March 2013 / Revised: 2 April 2013 / Accepted: 9 April 2013 / Published: 16 April 2013
Cited by 2 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We explored the contribution of nitrosamine metabolism to lung cancer in a pilot investigation of genetic variation in CYP2B6, a high-affinity enzymatic activator of tobacco-specific nitrosamines with a negligible role in nicotine metabolism. Previously we found that variation in CYP2A6 and [...] Read more.
We explored the contribution of nitrosamine metabolism to lung cancer in a pilot investigation of genetic variation in CYP2B6, a high-affinity enzymatic activator of tobacco-specific nitrosamines with a negligible role in nicotine metabolism. Previously we found that variation in CYP2A6 and CHRNA5-CHRNA3-CHRNB4 combined to increase lung cancer risk in a case-control study in European American ever-smokers (n = 860). However, these genes are involved in the pharmacology of both nicotine, through which they alter smoking behaviours, and carcinogenic nitrosamines. Herein, we separated participants by CYP2B6 genotype into a high- vs. low-risk group (*1/*1 + *1/*6 vs. *6/*6). Odds ratios estimated through logistic regression modeling were 1.25 (95% CI 0.68–2.30), 1.27 (95% CI 0.89–1.79) and 1.56 (95% CI 1.04–2.31) for CYP2B6, CYP2A6 and CHRNA5-CHRNA3-CHRNB4, respectively, with negligible differences when all genes were evaluated concurrently. Modeling the combined impact of high-risk genotypes yielded odds ratios that rose from 2.05 (95% CI 0.39–10.9) to 2.43 (95% CI 0.47–12.7) to 3.94 (95% CI 0.72–21.5) for those with 1, 2 and 3 vs. 0 high-risk genotypes, respectively. Findings from this pilot point to genetic variation in CYP2B6 as a lung cancer risk factor supporting a role for nitrosamine metabolic activation in the molecular mechanism of lung carcinogenesis Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)

Review

Jump to: Research

Open AccessReview Cancer Development, Progression, and Therapy: An Epigenetic Overview
Int. J. Mol. Sci. 2013, 14(10), 21087-21113; doi:10.3390/ijms141021087
Received: 30 August 2013 / Revised: 27 September 2013 / Accepted: 4 October 2013 / Published: 21 October 2013
Cited by 38 | PDF Full-text (692 KB) | HTML Full-text | XML Full-text
Abstract
Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, [...] Read more.
Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics. Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)

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