Lung and colorectal cancers are the most common types of cancer characterized by a poor prognosis and a high mortality rate. Mutations in the genes encoding components of the main intra- and extracellular signaling pathways, in particular the NOTCH1 gene (Notch1, a member of the Notch family of receptors), play one of the key roles in progression of these malignancies. Notch signaling is involved in maintaining homeostasis of the intestinal epithelium and structural and functional lung elements.
View Article and Find Full Text PDFHere we show that cancer stem cells amount in human lung adenocarcinoma cell line A549 depends on E-cadherin expression. In fact, downregulation of E-cadherin expression enhanced expression of pluripotent genes (c-MYC, NESTIN, OCT3/4 and SOX2) and enriched cell population with the cells possessing the properties of so-called 'cancer stem cells' via activation of Wnt/β-catenin signaling. Repression of E-cadherin also stimulated cell proliferation and migration in vitro, decreased cell amount essential for xenografts formation in nude mice, increased tumors vascularization and growth.
View Article and Find Full Text PDFHere we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation.
View Article and Find Full Text PDFOncogenes of the RAS family regulate many of the cell's activities, including proliferation, survival and differentiation. Activating mutations in these genes are common events for many types of cancer. One of the contradictory points concerning the biological significance of Ras activation is its dual effect (pro- or anti-proliferative) on cell reproduction.
View Article and Find Full Text PDFExperimental and clinical studies positively correlate expression of vascular endothelial growth factor (VEGF)-C in cancer cells with accelerated tumor progression and/or unfavorable clinical outcome. However, many aspects of tumor-promoting activity of VEGF-C and consequences of its downregulation for tumor progression remain poorly understood. To clarify these points, we created a set of VEGF receptor 3-positive lung carcinoma A549 and colon carcinoma HCT116 cell sublines with stable repression of VEGF-C synthesis.
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