a Usually, a single oncogene is not enough to turn a normal cell into a cancer cell, and many mutations in a number of different genes may be required to make a cell cancerous Ras Anchorage independent No tumor Myc Immortal No tumor Ras \Myc Anchorage- independent Tumor and immortal formation FIGURE 7-12 Synergy between oncogenes may be necessary to initiate malignant growth. A, The ras gene only. B, The myc gene only C, Synergy between ras and myc genes
Usually, a single oncogene is not enough to turn a normal cell into a cancer cell, and many mutations in a number of different genes may be required to make a cell cancerous
Survival Factors Growth Factors (e.g. IGF1) (e.g. interleukins, (e.g. TGFa, EGF) Extracellular Matri GPCR RTK RTK cdc42 PLC Grb2/sOs Fyn/Shc Dishevelled Src PKC Adenylate GSK-3B Akker MEK Hedgehog IKB MKK B-catenin (e.g, EPC) JAKs STAT5 Myc: -Ma Bcl-xL Max-Max ERK JNKs B-catenin: TCF Cytochrome C CyclO RbYCDK4 p15 Caspase 8 Apoptosis cycE←p27 ARF CDK2 Cel FADD mdm2 Bcl-2 ,ps3 (Proliferation mads (e.g. FasL, Tnf
肿瘤的信号转导通路调控异常
Motility Circuits Cytostasis and Differentiation Circuits ti-growth adjacent cells -+ E-cadherin e b-catenin TCF4- p16 extracellular-+integrins -O-O+O 0 Smads matrix Proliferation Circuits ↓99十 growth Ras→>0→ →O+chan DNA-damage in gene Hallmark senso -expression apabilities hormones→ ○-0 survival factors ○→0→0-0 abnormality factors sensor cvtokines Viability Circuits Figure 2. Intracellular Signaling Networks Regulate the Operations of the Cancer Cell. An elaborate integrated circuit operates within normal cells and is reprogrammed to regulate hallmark capabilities within cancer cells Separate subcircuits, depicted here in differently colored fields, are specialized to orchestrate the various capabilities. At one level, this depiction is simplistic, as there is considerable crosstalk such subcircuits addition, because each cancer cell is exposed to a complex mixture of signals from its microenvironment, each of these subcircuits is connected with signals originating from other cells in the tumor microenvironment,as outlined in Figure 5. (Hanahan D, Weinberg RA. hallmarks of Cancer: The Next Generation. Cell 2011, 144: 646)
Figure 2. Intracellular Signaling Networks Regulate the Operations of the Cancer Cell. An elaborate integrated circuit operates within normal cells and is reprogrammed to regulate hallmark capabilities within cancer cells. Separate subcircuits, depicted here in differently colored fields, are specialized to orchestrate the various capabilities. At one level, this depiction is simplistic, as there is considerable crosstalk between such subcircuits. In addition, because each cancer cell is exposed to a complex mixture of signals from its microenvironment, each of these subcircuits is connected with signals originating from other cells in the tumor microenvironment, as outlined in Figure 5. (Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell 2011, 144:646)
Oncogene Concept: An oncogene is a gene that when mutated or expressed at abnormally-high levels contributes to converting a normal cell into a cancer cell a Cellular oncogene(c-onc) proto-oncogene( proto-onc): in normal physiologic version Oncogene altered in cancer 口 iral oncogene(-onc
Oncogene Concept: An oncogene is a gene that when mutated or expressed at abnormally-high levels contributes to converting a normal cell into a cancer cell. Cellular oncogene (c-onc)： --- proto-oncogene （proto-onc）：in normal physiologic version --- Oncogene：altered in cancer Viral oncogene （v-onc）
Fuctions of proto-oncogenes r Proto-oncogenes have been identified at all levels of the various signal transduction cascades that control cell growth, proliferation and differentiation: e extracellular proteins function as growth factors o membrane proteins as cell surface receptors o cellular proteins that relay signals proteins in__nucleus, which activate the transcription and promote the cell cycle This signaling process involves a series of steps that o begin from the extracellular environment to cell membrane o involve a host of intermediaries in the cytoplasm end in the nucleus with the activation of transcription factors that help to move the cell through its growth cvcle
Proto-oncogenes have been identified at all levels of the various signal transduction cascades that control cell growth, proliferation and differentiation: extracellular proteins function as growth factors, membrane proteins as cell surface receptors cellular proteins that relay signals proteins in nucleus, which activate the transcription and promote the cell cycle This signaling process involves a series of steps that: begin from the extracellular environment to cell membrane; involve a host of intermediaries in the cytoplasm; end in the nucleus with the activation of transcription factors that help to move the cell through its growth cycle. Fuctions of proto-oncogenes