Partners in crime: The TGFβ and MAPK pathways in cancer progression

Cell and Bioscience

Volumn 1, Issue 1, 2011, Pages

  Chapnick, Douglas A ^a   Warner, Lisa ^a   Bernet, Jennifer ^b   Rao, Timsi ^a   Liu, Xuedong ^a  

^a Molecular and Cellular Biology   (United States)

^b UNIVERSITY OF COLORADO   (United States)

Author keywords

Crosstalk; ERK; MEK; Metastasis; Ras; Signal transduction; TGF

Indexed keywords

EID: 84862839654     PISSN: None     EISSN: 20453701     Source Type: Journal    
DOI: 10.1186/2045-3701-1-42     Document Type: Review

References (85)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011, 144(5):646-74. 10.1016/j.cell.2011.02.013, 21376230.
2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000, 100(1):57-70. 10.1016/S0092-8674(00)81683-9, 10647931.
3. Massague J. TGFbeta in Cancer. Cell 2008, 134(2):215-30. 10.1016/j.cell.2008.07.001, 18662538.
4. Massague J, Blain SW, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 2000, 103(2):295-309. 10.1016/S0092-8674(00)00121-5, 11057902.
5. Akhurst RJ, Derynck R. TGF-beta signaling in cancer--a double-edged sword. Trends Cell Biol 2001, 11(11):S44-51. 10.1016/S0962-8924(01)02130-4, 11684442.
6. Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 2003, 100(15):8621-8623. 10.1073/pnas.1633291100, 166359, 12861075.
7. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001, 29(2):117-29. 10.1038/ng1001-117, 11586292.
8. Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 1997, 9(2):180-6. 10.1016/S0955-0674(97)80061-0, 9069255.
9. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001, 410(6824):37-40. 10.1038/35065000, 11242034.
10. McKay MM, Morrison DK. Integrating signals from RTKs to ERK/MAPK. Oncogene 2007, 26(22):3113-21. 10.1038/sj.onc.1210394, 17496910.
11. van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol 1994, 10:251-337. 10.1146/annurev.cb.10.110194.001343, 7888178.
12. Friday BB, Adjei AA. Advances in targeting the Ras/Raf/MEK/Erk mitogen-activated protein kinase cascade with MEK inhibitors for cancer therapy. Clin Cancer Res 2008, 14(2):342-346. 10.1158/1078-0432.CCR-07-4790, 18223206.
13. Bhalla US, Ram PT, Iyengar R. MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network. Science 2002, 297(5583):1018-23. 10.1126/science.1068873, 12169734.
14. Biondi RM, Nebreda AR. Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions. Biochem J 2003, 372(Pt 1):1-13. 1223382, 12600273.
15. White MA, Anderson RG. Signaling networks in living cells. Annu Rev Pharmacol Toxicol 2005, 45:587-603. 10.1146/annurev.pharmtox.45.120403.095807, 15822190.
16. Nguyen A, et al. Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo. Mol Cell Biol 2002, 22(9):3035-3045. 10.1128/MCB.22.9.3035-3045.2002, 133772, 11940661.
17. Massague J. TGF-beta signal transduction. Annu Rev Biochem 1998, 67:753-91. 10.1146/annurev.biochem.67.1.753, 9759503.
18. Wrana JL, et al. Mechanism of activation of the TGF-beta receptor. Nature 1994, 370(6488):341-347. 10.1038/370341a0, 8047140.
19. Laiho M, Weis MB, Massague J. Concomitant loss of transforming growth factor (TGF)-beta receptor types I and II in TGF-beta-resistant cell mutants implicates both receptor types in signal transduction. J Biol Chem 1990, 265(30):18518-24.
20. Chen YG, Liu F, Massague J. Mechanism of TGFbeta receptor inhibition by FKBP12. Embo J 1997, 16(13):3866-76. 10.1093/emboj/16.13.3866, 1170011, 9233797.
21. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003, 113(6):685-700. 10.1016/S0092-8674(03)00432-X, 12809600.
22. Tsukazaki T, et al. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. Cell 1998, 95(6):779-91. 10.1016/S0092-8674(00)81701-8, 9865696.
23. Mullen AC, et al. Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-beta Signaling. Cell 2011, 147(3):565-76. 10.1016/j.cell.2011.08.050, 22036565.
24. Moustakas A, Heldin C-H. Non-Smad TGF-beta signals. J Cell Sci 2005, 118(Pt 16):3573-3584.
25. Mu Y, Gudey SK, Landstrom M. Non-Smad signaling pathways. Cell Tissue Res 2011,
26. Zhang YE. Non-Smad pathways in TGF-beta signaling. Cell Res 2009, 19(1):128-39. 10.1038/cr.2008.328, 2635127, 19114990.
27. Ikushima H, Miyazono K. Cellular context-dependent "colors" of transforming growth factor-beta signaling. Cancer Sci 2010, 101(2):306-12. 10.1111/j.1349-7006.2009.01441.x, 20067465.
28. Mulder KM. Role of Ras and Mapks in TGFbeta signaling. Cytokine Growth Factor Rev 2000, 11(1-2):23-35. 10.1016/S1359-6101(99)00026-X, 10708950.
29. Giehl K, Imamichi Y, Menke A. Smad4-independent TGF-beta signaling in tumor cell migration. Cells Tissues Organs 2007, 185(1-3):123-30. 10.1159/000101313, 17587818.
30. Parvani JG, Taylor MA, Schiemann WP. Noncanonical TGF-beta signaling during mammary tumorigenesis. J Mammary Gland Biol Neoplasia 2011, 16(2):127-46. 10.1007/s10911-011-9207-3, 21448580.
31. Lee MK, et al. TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J 2007, 26(17):3957-67. 10.1038/sj.emboj.7601818, 1994119, 17673906.
32. Zavadil J, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci USA 2001, 98(12):6686-6691. 10.1073/pnas.111614398, 34413, 11390996.
33. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006, 7(2):131-42. 10.1038/nrm1835, 16493418.
34. Sleeman JP, Thiery JP. SnapShot: The epithelial-mesenchymal transition. Cell 2011, 145(1):162 e1.
35. Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 2005, 24(37):5764-74. 10.1038/sj.onc.1208927, 16123809.
36. Cordenonsi M, et al. Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation. Science 2007, 315(5813):840-3. 10.1126/science.1135961, 17234915.
37. Samarakoon R, Higgins PJ. Integration of non-SMAD and SMAD signaling in TGF-beta1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells. Thromb Haemost 2008, 100(6):976-83. 2963177, 19132220.
38. Matsuura I, et al. Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry 2005, 44(37):12546-53. 10.1021/bi050560g, 16156666.
39. Kretzschmar M, et al. A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev 1999, 13(7):804-16. 10.1101/gad.13.7.804, 316599, 10197981.
40. Hayashida T, Decaestecker M, Schnaper HW. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells. FASEB J 2003, 17(11):1576-8.
41. Janda E, et al. Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J Cell Biol 2002, 156(2):299-313. 10.1083/jcb.200109037, 2199233, 11790801.
42. Funaba M, Zimmerman CM, Mathews LS. Modulation of Smad2-mediated signaling by extracellular signal-regulated kinase. J Biol Chem 2002, 277(44):41361-8. 10.1074/jbc.M204597200, 12193595.
43. Kfir S, et al. Pathway- and expression level-dependent effects of oncogenic N-Ras: p27(Kip1) mislocalization by the Ral-GEF pathway and Erk-mediated interference with Smad signaling. Mol Cell Biol 2005, 25(18):8239-50. 10.1128/MCB.25.18.8239-8250.2005, 1234306, 16135812.
44. Millet C, et al. A negative feedback control of transforming growth factor-beta signaling by glycogen synthase kinase 3-mediated Smad3 linker phosphorylation at Ser-204. J Biol Chem 2009, 284(30):19808-16. 10.1074/jbc.M109.016667, 2740406, 19458083.
45. Li F, et al. The linker region of Smad2 mediates TGF-beta-dependent ERK2-induced collagen synthesis. Biochem Biophys Res Commun 2009, 386(2):289-93. 10.1016/j.bbrc.2009.05.084, 19465000.
46. Wrighton KH, et al. Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling. J Biol Chem 2006, 281(50):38365-75. 10.1074/jbc.M607246200, 17035229.
47. Clarke DC, Liu X. Decoding the quantitative nature of TGF-beta/Smad signaling. Trends Cell Biol 2008, 18(9):430-42. 10.1016/j.tcb.2008.06.006, 2774497, 18706811.
48. Schmierer B, Hill CS. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 2007, 8(12):970-982. 10.1038/nrm2297, 18000526.
49. Sturm OE, et al. The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier. Sci Signal 2010, 3(153):ra90. 10.1126/scisignal.2001212, 21177493.
50. Ferrell JE. Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends Biochem Sci 1996, 21(12):460-6. 10.1016/S0968-0004(96)20026-X, 9009826.
51. Bhalla US, Iyengar R. Emergent properties of networks of biological signaling pathways. Science 1999, 283(5400):381-7. 10.1126/science.283.5400.381, 9888852.
52. Zi Z, et al. Quantitative analysis of transient and sustained transforming growth factor-beta signaling dynamics. Mol Syst Biol 2011, 7:492. 3130555, 21613981.
53. Jemal A, et al. Cancer statistics, 2010. CA Cancer J Clin 2010, 60(5):277-300. 10.3322/caac.20073, 20610543.
54. Xu Y, Pasche B. TGF-beta signaling alterations and susceptibility to colorectal cancer. Hum Mol Genet 2007, 16(Spec No 1):14-20.
55. Markowitz S, et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995, 268(5215):1336-8. 10.1126/science.7761852, 7761852.
56. Ogino S, et al. TGFBR2 mutation is correlated with CpG island methylator phenotype in microsatellite instability-high colorectal cancer. Hum Pathol 2007, 38(4):614-20. 10.1016/j.humpath.2006.10.005, 17270239.
57. Grady WM, et al. Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. Cancer Res 1999, 59(2):320-4.
58. Goggins M, et al. Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas. Cancer Res 1998, 58(23):5329-32.
59. Wang D, et al. Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer. Cancer Res 2000, 60(16):4507-12.
60. Pasche B, et al. TbetaR-I(6A) is a candidate tumor susceptibility allele. Cancer Res 1999, 59(22):5678-82.
61. Bian Y, et al. TGFBR1*6A may contribute to hereditary colorectal cancer. J Clin Oncol 2005, 23(13):3074-3078. 10.1200/JCO.2005.00.281, 15860866.
62. Skoglund J, et al. Lack of an association between the TGFBR1*6A variant and colorectal cancer risk. Clin Cancer Res 2007, 13(12):3748-3752. 10.1158/1078-0432.CCR-06-2865, 17575241.
63. Hahn SA, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996, 271(5247):350-3. 10.1126/science.271.5247.350, 8553070.
64. Takayama T, et al. Colorectal cancer: genetics of development and metastasis. J Gastroenterol 2006, 41(3):185-92. 10.1007/s00535-006-1801-6, 16699851.
65. Howe JR, et al. Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot. Am J Hum Genet 2002, 70(5):1357-1362. 10.1086/340258, 447611, 11920286.
66. Sweet K, et al. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA 2005, 294(19):2465-73. 10.1001/jama.294.19.2465, 16287957.
67. Ku J-L, et al. Genetic alterations of the TGF-beta signaling pathway in colorectal cancer cell lines: a novel mutation in Smad3 associated with the inactivation of TGF-beta-induced transcriptional activation. Cancer Lett 2007, 247(2):283-292. 10.1016/j.canlet.2006.05.008, 16828225.
68. Bello-DeOcampo D, Tindall DJ. TGF-betal/Smad signaling in prostate cancer. Curr Drug Targets 2003, 4(3):197-207. 10.2174/1389450033491118, 12643470.
69. de Caestecker MP, Piek E, Roberts AB. Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst 2000, 92(17):1388-1402. 10.1093/jnci/92.17.1388, 10974075.
70. Teraoka H, et al. Enhanced VEGF production and decreased immunogenicity induced by TGF-beta 1 promote liver metastasis of pancreatic cancer. Br J Cancer 2001, 85(4):612-617. 10.1054/bjoc.2001.1941, 2364097, 11506504.
71. Friedman E, et al. High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer. Cancer Epidemiol Biomarkers Prev 1995, 4(5):549-554.
72. Hjelmeland AB, et al. Loss of phosphatase and tensin homologue increases transforming growth factor beta-mediated invasion with enhanced SMAD3 transcriptional activity. Cancer Res 2005, 65(24):11276-11281. 10.1158/0008-5472.CAN-05-3016, 16357132.
73. Kakonen S-M, et al. Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways. J Biol Chem 2002, 277(27):24571-24578. 10.1074/jbc.M202561200, 11964407.
74. Kang Y, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3(6):537-49. 10.1016/S1535-6108(03)00132-6, 12842083.
75. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer 2005, 12(2):245-262. 10.1677/erc.1.0978, 15947100.
76. Sieben NLG, et al. In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours. J Pathol 2004, 202(3):336-340. 10.1002/path.1521, 14991899.
77. Brose MS, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002, 62(23):6997-7000.
78. Oft M, et al. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 1996, 10(19):2462-2477. 10.1101/gad.10.19.2462, 8843198.
79. Yu L, Hebert MC, Zhang YE. TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses. Embo J 2002, 21(14):3749-59. 10.1093/emboj/cdf366, 126112, 12110587.
80. Shirakihara T, et al. TGF-beta regulates isoform switching of FGF receptors and epithelial-mesenchymal transition. EMBO J 2011, 30(4):783-95. 10.1038/emboj.2010.351, 3041949, 21224849.
81. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 2005, 17(5):548-558. 10.1016/j.ceb.2005.08.001, 16098727.
82. Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007, 26(22):3291-3310. 10.1038/sj.onc.1210422, 17496923.
83. Yingling JM, Blanchard KL, Sawyer JS. Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov 2004, 3(12):1011-1022. 10.1038/nrd1580, 15573100.
84. Arteaga CL. Inhibition of TGFbeta signaling in cancer therapy. Curr Opin Genet Dev 2006, 16(1):30-37. 10.1016/j.gde.2005.12.009, 16377175.
85. Connolly EC, et al. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term TbetaRI/II kinase inhibition with LY2109761. Cancer Res 2011, 71(6):2339-49. 10.1158/0008-5472.CAN-10-2941, 21282335.