title: Signal transduction in cancer.
abstract: Cancer is driven by genetic and epigenetic alterations that allow cells to overproliferate and escape mechanisms that normally control their survival and migration. Many of these alterations map to signaling pathways that control cell growth and division, cell death, cell fate, and cell motility, and can be placed in the context of distortions of wider signaling networks that fuel cancer progression, such as changes in the tumor microenvironment, angiogenesis, and inflammation. Mutations that convert cellular proto-oncogenes to oncogenes can cause hyperactivation of these signaling pathways, whereas inactivation of tumor suppressors eliminates critical negative regulators of signaling. An examination of the PI3K-Akt and Ras-ERK pathways illustrates how such alterations dysregulate signaling in cancer and produce many of the characteristic features of tumor cells.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors.forename: Richard
authors.initials: R
authors.lastname: Sever
authors.affiliation: Harvard Medical School, Department of Cell Biology, Boston, Massachusetts 02115.
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
mesh_terms: D002465:Cell Movement; D016764:Cell Polarity; D049109:Cell Proliferation; D042822:Genomic Instability; D006801:Humans; D020935:MAP Kinase Signaling System; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D059016:Tumor Microenvironment
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
references.citation: Mol Cell. 2011 Feb 18;41(4):419-31
references.pmid: 21329880
references.citation: N Engl J Med. 2010 Dec 16;363(25):2424-33
references.pmid: 21067377
references.citation: PLoS One. 2010 Mar 09;5(3):e9616
references.pmid: 20231902
references.citation: Anticancer Res. 2008 Nov-Dec;28(6A):3613-9
references.pmid: 19189642
references.citation: Cell Cycle. 2005 Mar;4(3):365-7
references.pmid: 15701972
references.citation: Cold Spring Harb Perspect Biol. 2012 Oct 01;4(10):null
references.pmid: 23028116
references.citation: Cold Spring Harb Perspect Biol. 2012 Mar 01;4(3):null
references.pmid: 22383755
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5012-7
references.pmid: 20194747
references.citation: Oncogene. 2005 Nov 14;24(50):7443-54
references.pmid: 16288291
references.citation: Mol Cell Biol. 2004 Jul;24(13):5953-66
references.pmid: 15199149
references.citation: Genes Dev. 2000 Oct 1;14(19):2501-14
references.pmid: 11018017
references.citation: Hum Genet. 1996 Jun;97(6):714-9
references.pmid: 8641685
references.citation: Microbiol Mol Biol Rev. 2004 Jun;68(2):320-44
references.pmid: 15187187
references.citation: Cold Spring Harb Perspect Biol. 2012 Mar 01;4(3):null
references.pmid: 22296764
references.citation: J Biol Chem. 2013 Apr 12;288(15):10640-51
references.pmid: 23457334
references.citation: Cell. 2012 Sep 28;151(1):56-67
references.pmid: 23021215
references.citation: Cell. 2007 Sep 21;130(6):986-8
references.pmid: 17889643
references.citation: J Leukoc Biol. 2003 Jun;73(6):689-701
references.pmid: 12773501
references.citation: J Oncol. 2012;2012:951724
references.pmid: 22481935
references.citation: Mol Cell Biol. 2004 Jul;24(13):5923-36
references.pmid: 15199147
references.citation: Biochim Biophys Acta. 2011 Nov;1813(11):1978-86
references.pmid: 21440011
references.citation: Virus Res. 2002 Nov;89(2):213-28
references.pmid: 12445661
references.citation: FEBS J. 2010 Jan;277(1):2-21
references.pmid: 19843174
references.citation: Klin Onkol. 2011;24(1):41-5
references.pmid: 21539141
references.citation: Mol Biol Cell. 2007 Apr;18(4):1437-46
references.pmid: 17301289
references.citation: Nat Rev Cancer. 2011 Jul 22;11(8):597-608
references.pmid: 21779010
references.citation: Semin Cell Dev Biol. 2004 Apr;15(2):147-59
references.pmid: 15209374
references.citation: EMBO J. 2003 Jun 2;22(11):2788-97
references.pmid: 12773393
references.citation: Cold Spring Harb Perspect Biol. 2015 Dec 01;7(12 ):null
references.pmid: 26626938
references.citation: J Biol Chem. 2002 Sep 13;277(37):33895-900
references.pmid: 12107176
references.citation: FEBS J. 2013 May;280(9):2027-41
references.pmid: 23461856
references.citation: Nat Genet. 2013 Dec;45(12):1439-45
references.pmid: 24185512
references.citation: Mol Cell. 2012 Mar 9;45(5):598-609
references.pmid: 22306293
references.citation: Sci Signal. 2013 Jan 22;6(259):pe4
references.pmid: 23354686
references.citation: Nat Rev Genet. 2006 Aug;7(8):606-19
references.pmid: 16847462
references.citation: Nature. 2011 Apr 7;472(7341):90-4
references.pmid: 21399628
references.citation: Oncogene. 2005 Nov 14;24(50):7435-42
references.pmid: 16288290
references.citation: N Engl J Med. 2009 May 28;360(22):2289-301
references.pmid: 19474426
references.citation: Nat Med. 2010 Mar;16(3):286-94
references.pmid: 20154697
references.citation: Cell. 2010 Apr 30;141(3):432-45
references.pmid: 20434984
references.citation: Nat Med. 2013 Nov;19(11):1401-9
references.pmid: 24202393
references.citation: J Biol Chem. 2007 Apr 13;282(15):11221-9
references.pmid: 17287208
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Trends Endocrinol Metab. 2012 Feb;23(2):65-72
references.pmid: 22154484
references.citation: J Anim Ecol. 2013 Jan;82(1):182-90
references.pmid: 22943286
references.citation: Front Biosci (Landmark Ed). 2012 Jun 01;17:2616-43
references.pmid: 22652801
references.citation: Cancer Cell. 2012 Sep 11;22(3):389-403
references.pmid: 22975380
references.citation: Cold Spring Harb Perspect Med. 2013 Aug 01;3(8):null
references.pmid: 23906881
references.citation: Science. 2011 Dec 2;334(6060):1278-83
references.pmid: 22052977
references.citation: Cancer Res. 2013 Oct 15;73(20):6099-105
references.pmid: 24097826
references.citation: J Biol Chem. 2010 Jun 4;285(23):17673-80
references.pmid: 20356836
references.citation: Curr Opin Lipidol. 2012 Jun;23(3):226-34
references.pmid: 22449814
references.citation: J Mammary Gland Biol Neoplasia. 2011 Sep;16(3):205-19
references.pmid: 21822945
references.citation: Cell. 2013 Mar 28;153(1):56-69
references.pmid: 23540690
references.citation: J Biol Chem. 2013 Aug 16;288(33):23798-806
references.pmid: 23836898
references.citation: J Biomed Sci. 2013 Apr 18;20:24
references.pmid: 23594158
references.citation: Cancer Cell. 2012 Feb 14;21(2):227-39
references.pmid: 22340595
references.citation: Cell. 2011 May 27;145(5):732-44
references.pmid: 21620138
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-92
references.pmid: 22397650
references.citation: Nature. 2010 Jan 28;463(7280):545-8
references.pmid: 20072127
references.citation: Int J Mol Sci. 2012;13(8):9545-71
references.pmid: 22949815
references.citation: Bioorg Med Chem Lett. 2013 Jan 15;23(2):394-401
references.pmid: 23245516
references.citation: Nat Rev Cancer. 2010 Feb;10(2):102-15
references.pmid: 20094045
references.citation: PLoS One. 2013;8(1):e53752
references.pmid: 23359326
references.citation: Cells Tissues Organs. 2007;185(1-3):73-84
references.pmid: 17587811
references.citation: J Biol Chem. 2012 Jul 6;287(28):23698-709
references.pmid: 22619175
references.citation: Curr Pharm Des. 2014;20(15):2619-26
references.pmid: 23859617
references.citation: Cold Spring Harb Perspect Biol. 2012 Jun 01;4(6):null
references.pmid: 22661636
references.citation: Biochem J. 2005 Oct 1;391(Pt 1):87-93
references.pmid: 15971998
references.citation: Mol Biol Cell. 2002 Jul;13(7):2276-88
references.pmid: 12134068
references.citation: Nature. 2012 Nov 8;491(7423):254-8
references.pmid: 23034650
references.citation: Nature. 2012 Jan 11;481(7382):506-10
references.pmid: 22237025
references.citation: Apoptosis. 2009 Apr;14(4):348-63
references.pmid: 19212815
references.citation: J Pathol. 2013 Sep;231(1):21-34
references.pmid: 23780408
references.citation: Cell Rep. 2013 Sep 26;4(6):1116-30
references.pmid: 24055055
references.citation: Cold Spring Harb Perspect Biol. 2011 Dec 01;3(12):null
references.pmid: 21917992
references.citation: Biochem Biophys Res Commun. 1993 Oct 15;196(1):468-72
references.pmid: 8216329
references.citation: Cell Cycle. 2007 May 2;6(9):1024-9
references.pmid: 17426456
references.citation: Cold Spring Harb Perspect Biol. 2012 Nov 01;4(11):null
references.pmid: 23125017
references.citation: Cold Spring Harb Perspect Biol. 2012 May 01;4(5):null
references.pmid: 22550228
references.citation: Nat Rev Cancer. 2013 Oct;13(10):714-26
references.pmid: 24060863
references.citation: J Biol Chem. 1997 Aug 22;272(34):21281-8
references.pmid: 9261139
references.citation: Cell. 2013 Oct 10;155(2):397-409
references.pmid: 24120138
references.citation: Curr Opin Cell Biol. 2010 Dec;22(6):816-27
references.pmid: 20807678
references.citation: Cancer Discov. 2011 Aug;1(3):248-59
references.pmid: 22140653
references.citation: Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a011189
references.pmid: 22952397
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4610-5
references.pmid: 12668767
references.citation: Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a000141
references.pmid: 20066113
references.citation: Clin Cancer Res. 2012 Oct 15;18(20):5546-53
references.pmid: 23071356
references.citation: Cell. 2001 Feb 23;104(4):593-604
references.pmid: 11239415
references.citation: Cold Spring Harb Perspect Biol. 2012 Feb 01;4(2):null
references.pmid: 22129599
references.citation: Nat Rev Cancer. 2010 Feb;10(2):116-29
references.pmid: 20094046
references.citation: Nature. 2008 Mar 13;452(7184):181-6
references.pmid: 18337815
references.citation: Cell. 2012 Apr 27;149(3):656-70
references.pmid: 22541435
references.citation: Nat Cell Biol. 2002 Aug;4(8):556-64
references.pmid: 12134156
references.citation: Genes Dev. 1997 Apr 15;11(8):957-72
references.pmid: 9136925
references.citation: J Biol Chem. 1999 Dec 31;274(53):38083-90
references.pmid: 10608877
references.citation: Br J Biomed Sci. 2009;66(2):117-28
references.pmid: 19637655
references.citation: Cancer Cell. 2012 Mar 20;21(3):297-308
references.pmid: 22439925
references.citation: Cell. 2012 Feb 17;148(4):780-91
references.pmid: 22341448
references.citation: Cell. 2012 Mar 2;148(5):886-95
references.pmid: 22385958
references.citation: Science. 2013 Mar 29;339(6127):1567-70
references.pmid: 23539597
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7455-60
references.pmid: 20378837
references.citation: Future Oncol. 2009 Aug;5(6):811-25
references.pmid: 19663731
references.citation: Nat Rev Cancer. 2013 May;13(5):365-76
references.pmid: 23535846
references.citation: J Cell Biol. 2005 Mar 14;168(6):921-8
references.pmid: 15753124
references.citation: Mol Cell Biol. 2001 Aug;21(16):5644-57
references.pmid: 11463845
references.citation: Cell. 2012 Sep 28;151(1):68-79
references.pmid: 23021216
references.citation: J Clin Oncol. 2013 Nov 1;31(31):3987-96
references.pmid: 24101047
references.citation: Cancer Cell. 2012 Nov 13;22(5):601-14
references.pmid: 23153534
references.citation: Methods Mol Biol. 2011;769:1-24
references.pmid: 21748665
references.citation: Cell Adh Migr. 2011 May-Jun;5(3):211-4
references.pmid: 21519185
references.citation: Curr Opin Genet Dev. 2012 Feb;22(1):50-5
references.pmid: 22402447
references.citation: Cold Spring Harb Perspect Biol. 2015 Aug 03;7(8):a005959
references.pmid: 26238352
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Cold Spring Harb Perspect Biol. 2012 Aug 01;4(8):a011288
references.pmid: 22745287
references.citation: J Biol Chem. 2002 Jun 14;277(24):21843-50
references.pmid: 11923280
references.citation: J Cell Sci. 2013 Sep 1;126(Pt 17):3990-9
references.pmid: 23813956
references.citation: Cell. 2001 Jun 1;105(5):563-6
references.pmid: 11389825
references.citation: J Biol Chem. 1999 Jul 16;274(29):20281-6
references.pmid: 10400647
references.citation: Cold Spring Harb Perspect Biol. 2013 Mar 01;5(3):a008904
references.pmid: 23457258
references.citation: Nat Cell Biol. 2013 Feb;15(2):189-200
references.pmid: 23263278
references.citation: Nat Rev Cancer. 2013 Apr;13(4):246-57
references.pmid: 23467301
references.citation: Nat Genet. 2013 Dec;45(12):1446-51
references.pmid: 24185510
references.citation: Science. 2013 Mar 29;339(6127):1546-58
references.pmid: 23539594
references.citation: Biochem Pharmacol. 2013 Feb 15;85(4):449-65
references.pmid: 23103568
references.citation: Cold Spring Harb Perspect Biol. 2012 Jul 01;4(7):a006783
references.pmid: 22687276
references.citation: Sci Signal. 2009 Nov 17;2(97):ra73
references.pmid: 19920251
references.citation: Clin Cancer Res. 2010 Jul 1;16(13):3329-34
references.pmid: 20472680
references.citation: Steroids. 2004 Aug;69(8-9):517-22
references.pmid: 15288763
references.citation: Oncogene. 2008 Oct 9;27(46):5988-6001
references.pmid: 18641685
references.citation: Cold Spring Harb Perspect Biol. 2012 May 01;4(5):null
references.pmid: 22550232
references.citation: Biol Cell. 2009 Jan;101(1):13-29
references.pmid: 19055486
references.citation: Cold Spring Harb Perspect Biol. 2013 Mar 01;5(3):a016709
references.pmid: 23457262
references.citation: Dev Biol. 2004 Jan 1;265(1):23-32
references.pmid: 14697350
references.citation: EMBO J. 2012 Mar 7;31(5):1279-92
references.pmid: 22246185
references.citation: PLoS One. 2013 Sep 06;8(9):e74641
references.pmid: 24040302
references.citation: Nat Genet. 2012 Jan 29;44(3):251-3
references.pmid: 22286216
references.citation: Cold Spring Harb Perspect Biol. 2012 Oct 01;4(10):null
references.pmid: 23028119
references.citation: PLoS Biol. 2009 Jun 2;7(6):e1000121
references.pmid: 19492080
references.citation: Science. 2013 Mar 15;339(6125):1323-8
references.pmid: 23429703
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12054-9
references.pmid: 21730190
references.citation: EXS. 1995;74:1-15
references.pmid: 8527890
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7461-6
references.pmid: 20351271
references.citation: Genes Dev. 2013 Feb 15;27(4):355-71
references.pmid: 23431053
references.citation: Cancer Cell. 2013 Sep 9;24(3):365-78
references.pmid: 24029233
references.citation: Nat Rev Cancer. 2002 Jun;2(6):442-54
references.pmid: 12189386
references.citation: Front Mol Neurosci. 2011 Dec 02;4:51
references.pmid: 22144946