the-hallmarks-of-cancer(大牛的经典肿瘤学综述PPT).ppt

Paper sharing:Hanahan D, Weinberg R. Hallmarks of Cancer: The Next Generation.Cell, 2011,144( 5): 646-674. Dept. Medical Oncology, 1st Affiliated Hospital ****University Six hallmarks of cancer proposed in 2000 Emerging hallmarks Sustaining Proliferative Signaling The most fundamental trait of cancer cells involves their ability to sustain chronic proliferation Normal tissues ensuring a homeostasis by carefully control thing the production and release of growth-promoting signals Cancer cells, by deregulating these signals, become masters of their own destinies. The enabling signals are conveyed in large part by growth factors that bind cell-surface receptors Cancer cells can acquire the capability to sustain proliferative signaling in a number of alternative ways Cancer cells can produce growth factor ligands Send signals to stimulate normal cells within the supporting tumor-associated stroma Elevating the levels of receptor proteins displayed at the cancer cell surface Structural alterations in the receptor molecules Somatic mutations activate additional downstream pathways. EGFR mutation in NSCLC, B-Raf mutation in melanoma. Disruptions of negative-feedback mechanisms that attenuate proliferative signaling Excessive proliferative signaling can trigger cell senescence: RAS,MYC. Evading Growth Suppressors Cancer cells must circumvent powerful programs that negatively regulate cell proliferation Many of these programs depend on the actions of tumor suppressor genes Two prototypical tumor suppressors encode the RB and TP53 proteins To remove contact Inhibition Corruption of the TGF-b Pathway Promotes Malignancy, more elaborate than simple shutdown of its antiproliferative signaling circuitry activate EMT The RB protein integrates signals from diverse extracellular and intracellular sources and, in response, decides whether or not a cell should proceed through its growth-and-division cycle Cancer cells with defects in RB pathway functi