TAILIEUCHUNG - Chapter 080. Cancer Cell Biology and Angiogenesis (Part 12)

Figure 80-6 Oncogene signaling pathways are activated during tumor progression and promote metastatic potential. This figure shows a cancer cell that has undergone epithelial to mesenchymal transition (EMT) under the influence of several environmental signals. Critical components include activated transforming growth factor beta (TGF-β) and the hepatocyte growth factor (HGF)/c-Met pathways, as well as changes in the expression of adhesion molecules that mediate cell-cell and cellextracellular matrix interactions. Important changes in gene expression are mediated by the Snail and Twist family of transcriptional repressors (whose expression is induced by the oncogenic pathways), leading to reduced expression of E-cadherin, a key component. | Chapter 080. Cancer Cell Biology and Angiogenesis Part 12 Figure 80-6 Oncogene signaling pathways are activated during tumor progression and promote metastatic potential. This figure shows a cancer cell that has undergone epithelial to mesenchymal transition EMT under the influence of several environmental signals. Critical components include activated transforming growth factor beta TGF-0 and the hepatocyte growth factor HGF c-Met pathways as well as changes in the expression of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. Important changes in gene expression are mediated by the Snail and Twist family of transcriptional repressors whose expression is induced by the oncogenic pathways leading to reduced expression of E-cadherin a key component of adherens junctions between epithelial cells. This in conjunction with upregulation of N-cadherin a change in the pattern of expression of integrins which mediate cell-extracellular matrix associations that are important for cell motility and a switch in intermediate filament expression from cytokeratin to vimentin results in the phenotypic change from adherent highly organized epithelial cells to motile and invasive cells with a fibroblast or mesenchymal morphology. EMT is thought to be an important step leading to metastasis in some human cancers. Host stromal cells including tumor-associated fibroblasts and macrophages play an important role in modulating tumor cell behavior through secretion of growth factors and proangiogenic cytokines and matrix metalloproteinases that degrade the basement membrane. VEGF-A -C and -D are produced by tumor cells and stromal cells in response to hypoxia or oncogenic signals and induce production of new blood vessels and lymphatic channels through which tumor cells metastasize to lymph nodes or tissues. The metastatic phenotype may be a characteristic of all cells constituting the primary tumor however it is likely that variants with metastatic .

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