癌症生物学(英文版)

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The Hallmarks of Cancer
• 1. Sustaining proliferative signaling • 2. Evading growth suppressors • 3. Resisting cell death • 4. Enabling replicative immortality • 5. Inducing angiogenesis • 6. Activating invasion and metastasis • 7. Deregulating cellular energetics • 8. Avoiding immune destruction
factor • 5. Constitutive activation of signaling proteins downstream from the
receptor

2. Evading growth suppressors
• Cancer cells must overcome programs that negatively regulate cell proliferation
• Hallmarks of Cancer are eight, acquired, functional capabilities that allow cancer cells to survive, proliferate and disseminate
• First proposed by Hanahan and Weinberg in 2000 • Updated and expanded by Hanahan and Weinberg (Cell, 2011)
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1. Sustaining proliferative signaling
• Cancer cells need to sustain chronic proliferation • Growth promoting signals are normally conveyed by growth factors
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Evading growth suppressors
• RB protein integrates extracellular and intracellular signals to decide whether the cells should proceed thru growth and division
stimulation) • 2. Stimulate nearby normal (stromal) cells to produce growth factors • 3. Increased levels of cell surface receptor proteins • 4. Structurally abnormal receptors, active in the absence of growth
The Biology of Cancer
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The Hallmarks of Cancer
• A conceptual framework for understanding the biological diversity of cancer and to understanding the multistep process of progression from normal cells to a neoplastic state
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Growth factor receptor with tyrosine kinase
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Sustaining proliferative signaling
• Mechanisms to sustain proliferative signaling: • 1. Cancer cells produce growth factors themselves (autocrine
• Loss of RB function (by deletion or mutation) removes a gatekeeper of cell cycle progression resulting in persistent cell proliferation
• p53 protein senses intracellular stress and abnormality • If DNA damage is present or if growth promoting signals, oxygen or
binding to cell surface receptors which typically contain intracellular tyrosine kinase domains • The tyrosine kinase domain transmits signals via downstream signaling protein pathways to control progression through the cell cycle, cell growth and to influence cell survival and energy metabolism
• These programs depend on the action of tumor suppressor genes that normally govern the decision of cells to proliferate or to undergo program cell death (apoptosis)
• Tumor suppressor genes have typically been discovered when inactivation leads to the development of cancer
• The retinoblastoma (RB) protein and p53 protein are two tumor suppressors (among many described)