https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Integrins: versatility, modulation, and signaling in cell adhesion.

https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

/pdf/the-basics-of-epithelial-mesenchymal-transition-xe9crzoewf.pdf

The basics of epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) is a major process controlling multiple developmental events. The mesenchyme appeared as a transient state in diploblasts more than 800 million years ago. EMT has been conserved through evolution to control morphogenetic events, such as the formation of the three primary germ layers during gastrulation. Interestingly, related signal transduction pathways are remarkably conserved in many species. In the animal kingdom, EMT controls the intercellular adhesion machinery and its associated cytoskeleton. EMT pathways are also intimately involved in determination and differentiation programs, and are reactivated in adult tissues following injury or exposure to toxic agents. EMT is likely to play a role in early steps of carcinoma invasion, enabling blood or lymph vessel intravasation. Mesenchymal-like carcinoma cells undergo a mesenchymal to epithelial transition at distant sites from the primary tumor, and eventually form macrometastases. The mesenchymal-like state of cancer cells confers stemness, protection from cell death, immune escape and, most importantly, resistance to conventional and targeted therapies. Current strategies based on the EMT concept are aimed at designing new therapeutic approaches that interfere with the plasticity of carcinoma cells.

[Epithelial-mesenchymal transitions in cancer onset and progression].

SUMMARY In amphibian embryos, fibronectin (FN) assembles as a fibrillar network on the roof of the blastocoel cavity, preceding mesodermal cell migration. Local inversion of the ectoderm to produce a site where no FN is available prevents mesodermal cell migration. Microinjection of monovalent antibodies to FN arrests gastrulation. A complete inhibition of mesodermal cell migration is obtained after microinjection of a synthetic peptide containing the cell binding site sequence of FN. Prevention of interactions between receptors and FN appears to be the primary cause for blockage of gastrulation.

Evidence for the role of fibronectin in amphibian

We have previously reported activating mutations of the gene coding for the fibroblast growth factor receptor 3 (FGFR3) in invasive cervical carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we extended our study to screen a total of 75 invasive tumors and 80 cervical intraepithelial neoplasias (40 low-grade and 40 high-grade lesions). Using single strand conformation polymorphism (SSCP) followed by DNA sequencing, we found FGFR3 mutation (S249C in all cases) in 5% of invasive cervical carcinomas and no mutation in intraepithelial lesions. These results suggest that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02), and were more likely to be associated with a non-16/18 HPV type in their tumor. Gene expression analysis demonstrated that FGFR3 mutated tumors were associated with higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors. Supervised analysis of Affymetrix expression data identified a significant number of genes specifically differentially expressed in tumors with respect to FGFR3 mutation status. This study suggest that tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening.

/pdf/clinical-and-biological-characteristics-of-cervical-1z5mvlsgbm.pdf

Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Discovery of novel therapeutic opportunities for EOC is important for the improvement of clinical outcome of the patients. Emerging evidence is suggesting that epithelial-mesenchymal transition (EMT) plays a crucial role in the aggressiveness in EOC including increasing migration and invasion ability, contributing to chemoresistance and cancer stem cell populations. Targeting EMT in EOC thus offers an attractive therapeutic option.

Targeting pathways contributing to epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer.

Cadherins, a family of Ca-dependent adhesion molecules, have been proposed to act as regulators of morphogenetic processes and to be major effectors in the maintenance of tissue integrity. In this study, we have compared the effects of the expression of two truncated cadherins during early neurogenesis in Xenopus laevis. mRNA encoding deleted forms of XB- and N-cadherin lacking most of the extracellular domain were injected into the four animal dorsal blastomeres of 32-cell stage Xenopus embryos. These truncated cadherins altered the cohesion of cells derived from the injected blastomeres and induced morphogenetic defects in the anterior neural tissue to which they chiefly contributed. Truncated XB-cadherin was more efficient than N-cadherin in inducing these perturbations. Moreover, the coexpression of both truncated cadherins had additive perturbation effects on neural development. The two truncated cadherins can interact with the three known catenins, but with distinct affinities. These results suggest that the adhesive signal mediated by cadherins can be perturbed by overexpressing their cytoplasmic domains by competing with different affinity with catenins and/or a common anchor structure. Therefore, the correct regulation of cadherin function through the cytoplasmic domain appears to be a crucial step in the formation of the neural tissue.

/pdf/differential-perturbations-in-the-morphogenesis-of-anterior-1j5iqvxky0.pdf

Jean Paul Thiery

Papers

[Epithelial-mesenchymal transitions in cancer onset and progression].

Evidence for the role of fibronectin in amphibian

Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation

Targeting pathways contributing to epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer.

Differential perturbations in the morphogenesis of anterior structures induced by overexpression of truncated XB- and N-cadherins in Xenopus embryos.