Deconstructing networks of p53-mediated tumor suppression in vivo

Cell Death and Differentiation

Volumn 25, Issue 1, 2018, Pages 93-103

  Kaiser, Alyssa M ^a   Attardi, Laura D ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN P53;

CANCER INHIBITION; CELL CYCLE ARREST; DNA DAMAGE; DOWN REGULATION; FERROPTOSIS; GENE EXPRESSION; GENE TARGETING; HUMAN; IN VIVO STUDY; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SENESCENCE; STEM CELL; TRANSCRIPTION INITIATION; TUMOR MICROENVIRONMENT; TUMOR SUPPRESSOR GENE; ANIMAL; CELL AGING; CELL CYCLE CHECKPOINT; DNA REPAIR; EXPERIMENTAL NEOPLASM; GENETICS; KNOCKOUT MOUSE; METABOLISM; MOUSE; PATHOLOGY; PHYSIOLOGY;

ANIMALS; CELL CYCLE CHECKPOINTS; CELLULAR SENESCENCE; DNA REPAIR; MICE; MICE, KNOCKOUT; NEOPLASMS, EXPERIMENTAL; TRANSCRIPTIONAL ACTIVATION; TUMOR SUPPRESSOR PROTEIN P53;

EID: 85042169410     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/cdd.2017.171     Document Type: Review

References (120)

1. Vousden KH, Prives C. Blinded by the light: The growing complexity of p53. Cell 2009; 137: 413-431.
2. Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 2014; 14: 359-370.
3. Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010; 2: A001008.
4. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr., Butel JS et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356: 215-221.
5. Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson RT et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol 1994; 4: 1-7.
6. Malkin D, Li FP, Strong LC, Fraumeni JF Jr., Nelson CE, Kim DH et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250: 1233-1238.
7. Schmitt CA, McCurrach ME, de Stanchina E, Wallace-Brodeur RR, Lowe SW. INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes Dev 1999; 13: 2670-2677.
8. Eischen CM, Weber JD, Roussel MF, Sherr CJ, Cleveland JL. Disruption of the ARFMdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev 1999; 13: 2658-2669.
9. Jackson EL, Olive KP, Tuveson DA, Bronson R, Crowley D, Brown M et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res 2005; 65: 10280-10288.
10. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005; 7: 469-483.
11. Kenzelmann Broz D, Attardi LD. In vivo analysis of p53 tumor suppressor function using genetically engineered mouse models. Carcinogenesis 2010; 31: 1311-1318.
12. Giaccia AJ, Kastan MB. The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev 1998; 12: 2973-2983.
13. Horn HF, Vousden KH. Coping with stress: Multiple ways to activate p53. Oncogene 2007; 26: 1306-1316.
14. Hu W, Feng Z, Levine AJ. The regulation of multiple p53 stress responses is mediated through MDM2. Genes Cancer 2012; 3: 199-208.
15. Brady CA, Attardi LD. p53 at a glance. J Cell Sci 2010; 123(Pt 15): 2527-2532.
16. Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 2004; 119: 847-860.
17. Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM et al. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 2004; 119: 861-872.
18. Brady CA, Jiang D, Mello SS, Johnson TM, Jarvis LA, Kozak MM et al. Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 2011; 145: 571-583.
19. Johnson TM, Hammond EM, Giaccia A, Attardi LD. The p53QS transactivation-deficient mutant shows stress-specific apoptotic activity and induces embryonic lethality. Nat Genet 2005; 37: 145-152.
20. Candau R, Scolnick DM, Darpino P, Ying CY, Halazonetis TD, Berger SL. Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity. Oncogene 1997; 15: 807-816.
21. Venot C, Maratrat M, Sierra V, Conseiller E, Debussche L. Definition of a p53 transactivation function-deficient mutant and characterization of two independent p53 transactivation subdomains. Oncogene 1999; 18: 2405-2410.
22. Zhu J, Zhou W, Jiang J, Chen X. Identification of a novel p53 functional domain that is necessary for mediating apoptosis. J Biol Chem 1998; 273: 13030-13036.
23. Jiang D, Brady CA, Johnson TM, Lee EY, Park EJ, Scott MP et al. Full p53 transcriptional activation potential is dispensable for tumor suppression in diverse lineages. Proc Natl Acad Sci USA 2011; 108: 17123-17128.
24. Lane DP. Cancer. p53, guardian of the genome. Nature 1992; 358: 15-16.
25. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51(23 Pt 1): 6304-6311.
26. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817-825.
27. Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiationinduced cell cycle arrest compromised by p21 deficiency. Nature 1995; 377: 552-557.
28. Deng C, Zhang P, Harper JW, Elledge SJ, Leder P. Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell 1995; 82: 675-684.
29. Doumont G, Martoriati A, Beekman C, Bogaerts S, Mee PJ, Bureau F et al. G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. EMBO J 2005; 24: 3093-3103.
30. Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 1992; 71: 587-597.
31. Hollander MC, Sheikh MS, Bulavin DV, Lundgren K, Augeri-Henmueller L, Shehee R et al. Genomic instability in Gadd45a-deficient mice. Nat Genet 1999; 23: 176-184.
32. Lowe SW, Ruley HE, Jacks T, Housman DE. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993; 74: 957-967.
33. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. p53 is required for radiationinduced apoptosis in mouse thymocytes. Nature 1993; 362: 847-849.
34. Debbas M, White E. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev 1993; 7: 546-554.
35. Michalak EM, Jansen ES, Happo L, Cragg MS, Tai L, Smyth GK et al. Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death Differ 2009; 16: 684-696.
36. Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene 2003; 22: 9030-9040.
37. Martin-Caballero J, Flores JM, Garcia-Palencia P, Serrano M. Tumor susceptibility of p21 (Waf1/Cip1)-deficient mice. Cancer Res 2001; 61: 6234-6238.
38. Adnane J, Jackson RJ, Nicosia SV, Cantor AB, Pledger WJ, Sebti SM. Loss of p21WAF1/CIP1 accelerates Ras oncogenesis in a transgenic/knockout mammary cancer model. Oncogene 2000; 19: 5338-5347.
39. Young NP, Crowley D, Jacks T. Uncoupling cancer mutations reveals critical timing of p53 loss in sarcomagenesis. Cancer Res 2011; 71: 4040-4047.
40. Tront JS, Hoffman B, Liebermann DA. Gadd45a suppresses Ras-driven mammary tumorigenesis by activation of c-Jun NH2-terminal kinase and p38 stress signaling resulting in apoptosis and senescence. Cancer Res 2006; 66: 8448-8454.
41. Hildesheim J, Bulavin DV, Anver MR, Alvord WG, Hollander MC, Vardanian L et al. Gadd45a protects against UV irradiation-induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53. Cancer Res 2002; 62: 7305-7315.
42. Liu G, Parant JM, Lang G, Chau P, Chavez-Reyes A, El-Naggar AK et al. Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nat Genet 2004; 36: 63-68.
43. Timofeev O, Schlereth K,Wanzel M, Braun A, Nieswandt B, Pagenstecher A et al. p53 DNA binding cooperativity is essential for apoptosis and tumor suppression in vivo. Cell Rep 2013; 3: 1512-1525.
44. Barboza JA, Liu G, Ju Z, El-Naggar AK, Lozano G. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci USA 2006; 103: 19842-19847.
45. Artandi SE, DePinho RA. A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr Opin Genet Dev 2000; 10: 39-46.
46. Cosme-Blanco W, Shen MF, Lazar AJ, Pathak S, Lozano G, Multani AS et al. Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep 2007; 8: 497-503.
47. Post SM, Quintas-Cardama A, Terzian T, Smith C, Eischen CM, Lozano G. p53-dependent senescence delays Emu-myc-induced B-cell lymphomagenesis. Oncogene 2010; 29: 1260-1269.
48. Dankort D, Filenova E, Collado M, Serrano M, Jones K, McMahon M. A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Dev 2007; 21: 379-384.
49. Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M et al. Tumour biology: Senescence in premalignant tumours. Nature 2005; 436: 642.
50. Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 2005; 436: 725-730.
51. Symonds H, Krall L, Remington L, Saenz-Robles M, Lowe S, Jacks T et al. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 1994; 78: 703-711.
52. Yin C, Knudson CM, Korsmeyer SJ, Van Dyke T. Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 1997; 385: 637-640.
53. Lowe SW, Jacks T, Housman DE, Ruley HE. Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Proc Natl Acad Sci USA 1994; 91: 2026-2030.
54. Schmitt CA, Fridman JS, Yang M, Baranov E, Hoffman RM, Lowe SW. Dissecting p53 tumor suppressor functions in vivo. Cancer Cell 2002; 1: 289-298.
55. Eischen CM, Roussel MF, Korsmeyer SJ, Cleveland JL. Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol Cell Biol 2001; 21: 7653-7662.
56. Dansen TB, Whitfield J, Rostker F, Brown-Swigart L, Evan GI. Specific requirement for Bax, not Bak, in Myc-induced apoptosis and tumor suppression in vivo. J Biol Chem 2006; 281: 10890-10895.
57. Hemann MT, Zilfou JT, Zhao Z, Burgess DJ, Hannon GJ, Lowe SW. Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci USA 2004; 101: 9333-9338.
58. Beaudry VG, Jiang D, Dusek RL, Park EJ, Knezevich S, Ridd K et al. Loss of the p53/p63 regulated desmosomal protein Perp promotes tumorigenesis. PLoS Genet 2010; 6: E1001168.
59. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005; 434: 864-870.
60. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005; 434: 907-913.
61. Christophorou MA, Martin-Zanca D, Soucek L, Lawlor ER, Brown-Swigart L, Verschuren EW et al. Temporal dissection of p53 function in vitro and in vivo. Nat Genet 2005; 37: 718-726.
62. Christophorou MA, Ringshausen I, Finch AJ, Swigart LB, Evan GI. The pathological response to DNA damage does not contribute to p53-mediated tumour suppression. Nature 2006; 443: 214-217.
63. Hinkal G, Parikh N, Donehower LA. Timed somatic deletion of p53 in mice reveals ageassociated differences in tumor progression. PLoS ONE 2009; 4: E6654.
64. Efeyan A, Garcia-Cao I, Herranz D, Velasco-Miguel S, Serrano M. Tumour biology: Policing of oncogene activity by p53. Nature 2006; 443: 159.
65. Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y et al. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 2012; 149: 1269-1283.
66. Li T, Liu X, Jiang L, Manfredi J, Zha S, Gu W. Loss of p53-mediated cell-cycle arrest, senescence and apoptosis promotes genomic instability and premature aging. Oncotarget 2016; 7: 11838-11849.
67. Valente LJ, Gray DH, Michalak EM, Pinon-Hofbauer J, Egle A, Scott CL et al. p53 efficiently suppresses tumor development in the complete absence of its cell-cycle inhibitory and proapoptotic effectors p21, Puma, and Noxa. Cell Rep 2013; 3: 1339-1345.
68. Bieging-Rolett KT, Johnson TM, Brady CA, Beaudry VG, Pathak N, Han S et al. p19(Arf) is required for the cellular response to chronic DNA damage. Oncogene 2016; 35: 4414-4421.
69. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012; 149: 1060-1072.
70. Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol 2014; 10: 9-17.
71. Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 2015; 520: 57-62.
72. Jennis M, Kung CP, Basu S, Budina-Kolomets A, Leu JI, Khaku S et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016; 30: 918-930.
73. Ou Y, Wang SJ, Li D, Chu B, Gu W. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. Proc Natl Acad Sci USA 2016; 113: E6806-E6812.
74. Wang SJ, Li D, Ou Y, Jiang L, Chen Y, Zhao Y et al. Acetylation is crucial for p53-mediated ferroptosis and tumor suppression. Cell Rep 2016; 17: 366-373.
75. Xie Y, Zhu S, Song X, Sun X, Fan Y, Liu J et al. The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep 2017; 20: 1692-1704.
76. Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol 2005; 7: 165-171.
77. Marion RM, Strati K, Li H, Murga M, Blanco R, Ortega S et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 2009; 460: 1149-1153.
78. Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP et al. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 2009; 462: 595-601.
79. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM et al. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 2009; 460: 1145-1148.
80. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O, Nakagawa M et al. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 2009; 460: 1132-1135.
81. Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 2009; 460: 1140-1144.
82. Choi YJ, Lin CP, Ho JJ, He X, Okada N, Bu P et al. miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nat Cell Biol 2011; 13: 1353-1360.
83. Pant V, Quinas-Cardama A, Lozano G. The p53 pathway in hematopoesis: Lessons from mouse models, implications for humans. Blood 2012; 120: 5118-5127.
84. Tao L, Roberts AL, Dunphy KA, Bigelow C, Yan H, Jerry DJ. Repression of mammary stem/progenitor cells by p53 is mediated by Notch and separable from apoptotic activity. Stem Cells 2011; 29: 119-127.
85. McConnell AM, Yao C, Yeckes AR, Wang Y, Selvaggio AS, Tang J et al. p53 regulates progenitor cell quiescence and differentiation in the airway. Cell Rep 2016; 17: 2173-2182.
86. Zhao Z, Zuber J, Diaz-Flores E, Lintault L, Kogan SC, Shannon K et al. p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal. Genes Dev 2010; 24: 1389-1402.
87. Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ et al. p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 2008; 455: 1129-1133.
88. Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: A lifeguard with a licence to kill. Nat Rev Mol Cell Biol 2015; 16: 393-405.
89. Cheung EC, Athineos D, Lee P, Ridgway RA, Lambie W, Nixon C et al. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev Cell 2013; 25: 463-477.
90. Zaugg K, Yao Y, Reilly PT, Kannan K, Kiarash R, Mason J et al. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev 2011; 25: 1041-1051.
91. Jiang D, LaGory EL, Kenzelmann Broz D, Bieging KT, Brady CA, Link N et al. Analysis of p53 transactivation domain mutants reveals Acad11 as a metabolic target important for p53 pro-survival function. Cell Rep 2015; 10: 1096-1109.
92. Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res 2010; 44: 479-496.
93. Cano CE, Gommeaux J, Pietri S, Culcasi M, Garcia S, Seux M et al. Tumor protein 53-induced nuclear protein 1 is a major mediator of p53 antioxidant function. Cancer Res 2009; 69: 219-226.
94. Al Saati T, Clerc P, Hanoun N, Peuget S, Lulka H, Gigoux V et al. Oxidative stress induced by inactivation of TP53INP1 cooperates with KrasG12D to initiate and promote pancreatic carcinogenesis in the murine pancreas. Am J Pathol 2013; 182: 1996-2004.
95. Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM. The antioxidant function of the p53 tumor suppressor. Nat Med 2005; 11: 1306-1313.
96. White E. The role for autophagy in cancer. J Clin Invest 2015; 125: 42-46.
97. Kenzelmann Broz D, Spano Mello S, Bieging KT, Jiang D, Dusek RL, Brady CA et al. Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses. Genes Dev 2013; 27: 1016-1031.
98. Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature 2013; 504: 296-300.
99. Rao S, Tortola L, Perlot T, Wirnsberger G, Novatchkova M, Nitsch R et al. A dual role for autophagy in a murine model of lung cancer. Nat Commun 2014; 5: 3056.
100. Strohecker AM, Guo JY, Karsli-Uzunbas G, Price SM, Chen GJ, Mathew R et al. Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors. Cancer Discov 2013; 3: 1272-1285.
101. Hollander MC, Philburn RT, Patterson AD, Velasco-Miguel S, Friedberg EC, Linnoila RI et al. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proc Natl Acad Sci USA 2005; 102: 13200-13205.
102. Friedberg EC, Bond JP, Burns DK, Cheo DL, Greenblatt MS, Meira LB et al. Defective nucleotide excision repair in xpc mutant mice and its association with cancer predisposition. Mutat Res 2000; 459: 99-108.
103. Melis JP, Wijnhoven SW, Beems RB, Roodbergen M, van den Berg J, Moon H et al. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes. Cancer Res 2008; 68: 1347-1353.
104. Yoon T, Chakrabortty A, Franks R, Valli T, Kiyokawa H, Raychaudhuri P. Tumor-prone phenotype of the DDB2-deficient mice. Oncogene 2005; 24: 469-478.
105. Gordon DJ, Resio B, Pellman D. Causes and consequences of aneuploidy in cancer. Nat Rev Genet 2012; 13: 189-203.
106. Thompson SL, Compton DA. Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J Cell Biol 2010; 188: 369-381.
107. Dudgeon C, Chan C, Kang W, Sun Y, Emerson R, Robins H et al. The evolution of thymic lymphomas in p53 knockout mice. Genes Dev 2014; 28: 2613-2620.
108. Muller PA, Vousden KH, Norman JC. p53 and its mutants in tumor cell migration and invasion. J Cell Biol 2011; 192: 209-218.
109. Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol 2011; 195: 417-433.
110. Chang CJ, Chao CH, Xia W, Yang JY, Xiong Y, Li CW et al. p53 regulates epithelialmesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 2011; 13: 317-323.
111. Wang SP, Wang WL, Chang YL, Wu CT, Chao YC, Kao SH et al. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nat Cell Biol 2009; 11: 694-704.
112. Caswell DR, Chuang CH, Yang D, Chiou SH, Cheemalavagu S, Kim-Kiselak C et al. Obligate progression precedes lung adenocarcinoma dissemination. Cancer Discov 2014; 4: 781-789.
113. Dameron KM, Volpert OV, Tainsky MA, Bouck N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 1994; 265: 1582-1584.
114. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445: 656-660.
115. Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE et al. Non-cellautonomous tumor suppression by p53. Cell 2013; 153: 449-460.
116. Yoon KW, Byun S, Kwon E, Hwang SY, Chu K, Hiraki M et al. Control of signalingmediated clearance of apoptotic cells by the tumor suppress of p53. Science 2015; 349: 1261669.
117. Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 2002; 32: 355-357.
118. Paterson RF, Ulbright TM, MacLennan GT, Zhang S, Pan CX, Sweeney CJ et al. Molecular genetic alterations in the laser-capture-microdissected stroma adjacent to bladder carcinoma. Cancer 2003; 98: 1830-1836.
119. Hill R, Song Y, Cardiff RD, Van Dyke T. Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 2005; 123: 1001-1011.
120. Kiaris H, Chatzistamou I, Trimis G, Frangou-Plemmenou M, Pafiti-Kondi A, Kalofoutis A. Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis. Cancer Res 2005; 65: 1627-1630.