lec17 - CANCER AGEING and METABOLISM difficulties in being...

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Unformatted text preview: CANCER, AGEING and METABOLISM difficulties in being a long-lived MCO cancer ageing (quantity) (quality) cancer pathogens: differences are clearer cancer cells: differences are subtle what are other adaptive features of tumor cells? how are they different from normal cells? cell biology genomics proteomics metabolism fast-growing cells in midst of stationary cells remove front layer F F fast-growing cells in midst of stationary cells starved for oxygen lack of nutrients low O 2 causes transcriptional response hypoxia-inducible factor: HIF1- α fast-growing cells in midst of stationary cells low oxygen HIF1- α increased glycolysis angiogenic factors How is low oxygen sensed in mammalian cells? HIF1- α HIF1- α OH proline hydroxylase 2 degraded stable when O 2 is high, HIF is low when O 2 is low, HIF builds up Tumor vascularization is a critical step in cancer progression fast-growing cells in midst of stationary cells low oxygen HIF1- α increased glycolysis angiogenic factors what are the special features of tumor cell metabolism? “The prime cause of cancer is the replacement of the respiration of oxygen ... in normal body cells by fermentation of sugar” Otto Warburg 1956 Tumor cells derive nearly all of their fatty acids from de novo sythesis Sidney Weinhouse 1953 Craig Thompson, M.D. U. Penn Cancer Center is glucose-dependent FA synthesis an “achilles heel” of tumor cells? fig 21-10 remember citrate lyase? fig 21-10 citrate lyase as an anabolic carbon source… FA synthesis in glycolytic tumor cells pre-developed drugs......
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lec17 - CANCER AGEING and METABOLISM difficulties in being...

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