Skip to main content
SpringerLink
Log in
Book cover

Squamous cell Carcinoma pp 113–134Cite as

p53 in Head and Neck Squamous Cell Carcinoma

  • Chapter
  • First Online:

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and has a mortality rate of 50% despite surgery. The major risk factors associated with HNSCC are smoking, alcohol, and human papillomavirus (HPV). p53, a transcriptional factor, is the most commonly mutated protein in HNSCC and plays an important and early role in tumorigenesis. The chapter highlights the story of p53 in the progression and management of HNSCC. In particular, we address p53’s mutational landscape and its resultant phenotypic outcomes. In addition, p53 as a prognostic biomarker and predictive biomarker for clinical outcome is addressed. Finally, we discuss p53 as a druggable target in HNSCC patients. This chapter aims to expand the understanding of the role of p53 in HNSCC in order to improve management of HNSCC patients by providing them with a personalized and customizable treatment plan.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, Solari A, Bobisse S, Rondina MB, Guzzardo V, Parenti AR, Rosato A, Bicciato S, Balmain A, Piccolo S (2009) A mutant-p53/smad complex opposes p63 to empower TGFβ-induced metastasis. Cell 137(1):87–98. doi:10.1016/j.cell.2009.01.039

    Article  CAS  PubMed  Google Scholar 

  • Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie T-X, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Treviño L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333(6046):1154–1157. doi:10.1126/science.1206923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aloni-Grinstein R, Schwartz D, Rotter V (1995) Accumulation of wild-type p53 protein upon gamma-irradiation induces a G2 arrest-dependent immunoglobulin kappa light chain gene expression. EMBO J 14(7):1392–1401

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35. doi:10.1056/NEJMoa0912217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet (London, England) 371(9625):1695–1709. doi:10.1016/s0140-6736(08)60728-x

  • Balz V, Scheckenbach K, Götte K, Bockmühl U, Petersen I, Bier H (2003) Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2–11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens. Cancer Res 63(6):1188–1191

    CAS  PubMed  Google Scholar 

  • Berkers CR, Maddocks OD, Cheung EC, Mor I, Vousden KH (2013) Metabolic regulation by p53 family members. Cell Metab 18(5):617–633. doi:10.1016/j.cmet.2013.06.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, Agami R, Ge W, Cavet G, Linsley PS, Beijersbergen RL, Bernards R (2004) A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428(6981):431–437. doi:10.1038/nature02371

    Article  CAS  PubMed  Google Scholar 

  • Bond GL, Hu W, Levine A (2005) A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res 65(13):5481–5484. doi:10.1158/0008-5472.CAN-05-0825

    Article  CAS  PubMed  Google Scholar 

  • Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH (2003) A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res 63(8):1727–1730

    CAS  PubMed  Google Scholar 

  • Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR, Brakenhoff RH (2004) Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst 96(13):998–1006

    Article  CAS  PubMed  Google Scholar 

  • Bradford CR, Zhu S, Ogawa H, Ogawa T, Ubell M, Narayan A, Johnson G, Wolf GT, Fisher SG, Carey TE (2003) P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines. Head Neck 25(8):654–661. doi:10.1002/hed.10274

    Article  PubMed  Google Scholar 

  • Brosh R, Rotter V (2009) When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer 9(10):701–713. doi:10.1038/nrc2693

    CAS  PubMed  Google Scholar 

  • Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP (2009) Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 9(12):862–873. doi:10.1038/nrc2763

    Article  CAS  PubMed  Google Scholar 

  • Bullock AN, Henckel J, Fersht AR (2000) Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy. Oncogene 19(10):1245–1256. doi:10.1038/sj.onc.1203434

    Article  CAS  PubMed  Google Scholar 

  • Bykov VJ, Issaeva N, Shilov A, Hultcrantz M, Pugacheva E, Chumakov P, Bergman J, Wiman KG, Selivanova G (2002) Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 8(3):282–288. doi:10.1038/nm0302-282

    Article  CAS  PubMed  Google Scholar 

  • Cabelguenne A, Blons H, de Waziers I, Carnot F, Houllier AM, Soussi T, Brasnu D, Beaune P, Laccourreye O, Laurent-Puig P (2000) p53 alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series. J Clin Oncol Off J Am Soc Clin Oncol 18(7):1465–1473

    Article  CAS  Google Scholar 

  • Caicedo-Granados E, Lin R, Fujisawa C, Yueh B, Sangwan V, Saluja A (2014) Wild-type p53 reactivation by small-molecule Minnelide™ in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma. Oral Oncol 50(12):1149–1156. doi:10.1016/j.oraloncology.2014.09.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chuang HC, Yang LP, Fitzgerald AL, Osman A, Woo SH, Myers JN, Skinner HD (2014) The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells. PLoS ONE 9(8):e104821. doi:10.1371/journal.pone.0104821

    Article  PubMed  PubMed Central  Google Scholar 

  • Cimpean AM, Balica RA, Doros IC, Balica NC, Gaje PN, Popovici RA, Raica M (2016) Epidermal growth factor receptor (EGFR) and keratin 5 (K5): versatile keyplayers defining prognostic and therapeutic sub-classes of head and neck squamous cell carcinomas. Cancer Genom Proteom 13(1):75–81

    CAS  Google Scholar 

  • Clayman GL, el-Naggar AK, Lippman SM, Henderson YC, Frederick M, Merritt JA, Zumstein LA, Timmons TM, Liu TJ, Ginsberg L, Roth JA, Hong WK, Bruso P, Goepfert H (1998) Adenovirus-mediated p 53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 16 (6):2221–2232

    Google Scholar 

  • Csuka O, RemenÁr É, Koronczay K, Doleschall Z, NÉmeth G (1997) Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer. Pathol Oncol Res 3(3):204–210. doi:10.1007/bf02899922

    Article  CAS  PubMed  Google Scholar 

  • Davison TS, Vagner C, Kaghad M, Ayed A, Caput D, Arrowsmith CH (1999) p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53. J Biol Chem 274(26):18709–18714

    Article  CAS  PubMed  Google Scholar 

  • Di Agostino S, Cortese G, Monti O, Dell’Orso S, Sacchi A, Eisenstein M, Citro G, Strano S, Blandino G (2008) The disruption of the protein complex mutantp53/p 73 increases selectively the response of tumor cells to anticancer drugs. Cell Cycle (Georgetown, Tex) 7(21):3440–3447. doi:10.4161/cc.7.21.6995

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917. doi:10.1002/ijc.25516

    Article  CAS  PubMed  Google Scholar 

  • Foster BA, Coffey HA, Morin MJ, Rastinejad F (1999) Pharmacological rescue of mutant p53 conformation and function. Science 286(5449):2507–2510

    Article  CAS  PubMed  Google Scholar 

  • Freed-Pastor WA, Prives C (2012) Mutant p53: one name, many proteins. Genes Dev 26(12):1268–1286. doi:10.1101/gad.190678.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freed-Pastor WA, Mizuno H, Zhao X, Langerod A, Moon SH, Rodriguez-Barrueco R, Barsotti A, Chicas A, Li W, Polotskaia A, Bissell MJ, Osborne TF, Tian B, Lowe SW, Silva JM, Borresen-Dale AL, Levine AJ, Bargonetti J, Prives C (2012) Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell 148(1–2):244–258. doi:10.1016/j.cell.2011.12.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganly I, Kirn D, Eckhardt G, Rodriguez GI, Soutar DS, Otto R, Robertson AG, Park O, Gulley ML, Heise C, Von Hoff DD, Kaye SB (2000) A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res Off J Am Assoc Cancer Res 6(3):798–806

    CAS  Google Scholar 

  • Girardini JE, Napoli M, Piazza S, Rustighi A, Marotta C, Radaelli E, Capaci V, Jordan L, Quinlan P, Thompson A, Mano M, Rosato A, Crook T, Scanziani E, Means AR, Lozano G, Schneider C, Del Sal G (2011) A Pin1/mutant p53 axis promotes aggressiveness in breast cancer. Cancer Cell 20(1):79–91. doi:10.1016/j.ccr.2011.06.004

    Article  CAS  PubMed  Google Scholar 

  • Gottlieb E, Haffner R, von Ruden T, Wagner EF, Oren M (1994) Down-regulation of wild-type p53 activity interferes with apoptosis of IL-3-dependent hematopoietic cells following IL-3 withdrawal. EMBO J 13(6):1368–1374

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hainaut P, Hollstein M (2000) p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 77:81–137

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL (2006) Repression of p 53 activity by Smyd2-mediated methylation. Nature 444(7119):629–632. doi:http://www.nature.com/nature/journal/v444/n7119/suppinfo/nature05287_S1.html

  • Hussain SP, Harris CC (1998) Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes. Cancer Res 58(18):4023–4037

    CAS  PubMed  Google Scholar 

  • Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G (2004) Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 10(12):1321–1328. doi:10.1038/nm1146

    Article  CAS  PubMed  Google Scholar 

  • Iwakuma T, Parrales A (2015) Targeting oncogenic mutant p 53 for cancer therapy. Front Oncol 5. doi:10.3389/fonc.2015.00288

  • Katsonis P, Lichtarge O (2014) A formal perturbation equation between genotype and phenotype determines the evolutionary action of protein-coding variations on fitness. Genome Res 24(12):2050–2058. doi:10.1101/gr.176214.114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klussmann JP, Weissenborn SJ, Wieland U, Dries V, Kolligs J, Jungehuelsing M, Eckel HE, Dienes HP, Pfister HJ, Fuchs PG (2001) Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 92(11):2875–2884

    Article  CAS  PubMed  Google Scholar 

  • Lamont JP, Nemunaitis J, Kuhn JA, Landers SA, McCarty TM (2000) A prospective phase II trial of ONYX-015 adenovirus and chemotherapy in recurrent squamous cell carcinoma of the head and neck (the Baylor experience). Ann Surg Oncol 7(8):588–592

    Article  CAS  PubMed  Google Scholar 

  • Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358(6381):15–16. doi:10.1038/358015a0

    Article  CAS  PubMed  Google Scholar 

  • Lang GA, Iwakuma T, Suh Y-A, Liu G, Rao VA, Parant JM, Valentin-Vega YA, Terzian T, Caldwell LC, Strong LC, El-Naggar AK, Lozano G (2004) Gain of Function of a p53 Hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 119(6):861–872. doi:10.1016/j.cell.2004.11.006

    Article  CAS  PubMed  Google Scholar 

  • Leemans CR, Braakhuis BJM, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22

    Article  CAS  PubMed  Google Scholar 

  • Levine AJ, Wu MC, Chang A, Silver A, Attiyeh EF, Lin J, Epstein CB (1995) The spectrum of mutations at the p53 locus. Ann N Y Acad Sci 768(1):111–128. doi:10.1111/j.1749-6632.1995.tb12115.x

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Prives C (2007) Are interactions with p63 and p73 involved in mutant p53 gain of oncogenic function? Oncogene 26(15):2220–2225

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Li LJ, Zhang ST, Wang LJ, Zhang Z, Gao N, Zhang YY, Chen QM (2009) In vitro and clinical studies of gene therapy with recombinant human adenovirus-p53 injection for oral leukoplakia. Clin Cancer Res Off J Am Assoc Cancer Res 15(21):6724–6731. doi:10.1158/1078-0432.ccr-09-1296

    Article  CAS  Google Scholar 

  • Linares LK, Hengstermann A, Ciechanover A, Muller S, Scheffner M (2003) HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53. Proc Natl Acad Sci U S A 100(21):12009–12014. doi:10.1073/pnas.2030930100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu TJ, el-Naggar AK, McDonnell TJ, Steck KD, Wang M, Taylor DL, Clayman GL (1995) Apoptosis induction mediated by wild-type p 53 adenoviral gene transfer in squamous cell carcinoma of the head and neck. Cancer Res 55(14):3117–3122

    Google Scholar 

  • Liu K, Ling S, Lin WC (2011) TopBP1 mediates mutant p53 gain of function through NF-Y and p63/p73. Mol Cell Biol 31(22):4464–4481. doi:10.1128/mcb.05574-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marur S, D’Souza G, Westra WH, Forastiere AA (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11(8):781–789. doi:10.1016/s1470-2045(10)70017-6

    Article  PubMed  PubMed Central  Google Scholar 

  • Milner J, Medcalf EA (1991) Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell 65(5):765–774. doi:10.1016/0092-8674(91)90384-B

    Article  CAS  PubMed  Google Scholar 

  • Muller PAJ, Vousden KH (2013) p53 mutations in cancer. Nat Cell Biol 15(1):2–8

    Article  CAS  PubMed  Google Scholar 

  • Muller PAJ, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, Lukashchuk N, Gillespie DA, Ludwig RL, Gosselin P, Cromer A, Brugge JS, Sansom OJ, Norman JC, Vousden KH (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139(7):1327–1341. doi:10.1016/j.cell.2009.11.026

    Article  PubMed  Google Scholar 

  • Nemunaitis J, Nemunaitis J (2011) Head and neck cancer: response to p53-based therapeutics. Head Neck 33(1):131–134. doi:10.1002/hed.21364

    Article  PubMed  Google Scholar 

  • Nemunaitis J, Cunningham C, Buchanan A, Blackburn A, Edelman G, Maples P, Netto G, Tong A, Randlev B, Olson S, Kirn D (2001a) Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther 8(10):746–759. doi:10.1038/sj.gt.3301424

    Article  CAS  PubMed  Google Scholar 

  • Nemunaitis J, Khuri F, Ganly I, Arseneau J, Posner M, Vokes E, Kuhn J, McCarty T, Landers S, Blackburn A, Romel L, Randlev B, Kaye S, Kirn D (2001b) Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer. J Clin Oncol Off J Am Soc Clin Oncol 19(2):289–298

    Article  CAS  Google Scholar 

  • Neskey DM, Osman AA, Ow TJ, Katsonis P, McDonald T, Hicks SC, Hsu T-K, Pickering CR, Ward A, Patel A, Yordy JS, Skinner HD, Giri U, Sano D, Story MD, Beadle BM, El-Naggar AK, Kies MS, William WN, Caulin C, Frederick M, Kimmel M, Myers JN, Lichtarge O (2015) Evolutionary action score of TP53 identifies high-risk mutations associated with decreased survival and increased distant metastases in head and neck cancer. Cancer Res 75(7):1527–1536. doi:10.1158/0008-5472.can-14-2735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohnishi K, Ota I, Takahashi A, Ohnishi T (2000) Glycerol restores p53-dependent radiosensitivity of human head and neck cancer cells bearing mutant p53. Br J Cancer 83(12):1735–1739. doi:10.1054/bjoc.2000.1511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohnishi T, Ohnishi K, Takahashi A (2002) Glycerol restores heat-induced p53-dependent apoptosis of human glioblastoma cells bearing mutant p53. BMC Biotechnol 2:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohtomo-Oda R, Komatsu S, Mori T, Sekine S, Hirajima S, Yoshimoto S, Kanai Y, Otsuji E, Ikeda E, Tsuda H (2016) SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus–unrelated nonmultiple head and neck carcinomas. Hum Pathol 49:145–155. doi:10.1016/j.humpath.2015.08.025

    Article  CAS  PubMed  Google Scholar 

  • Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT, Crowley D, Jacks T (2004) Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119(6):847–860. doi:10.1016/j.cell.2004.11.004

    Article  CAS  PubMed  Google Scholar 

  • Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu T-K, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN (2015) Evolutionary action score of TP53 coding variants is predictive of platinum response in head and neck cancer patients. Cancer Res 75(7):1205–1215. doi:10.1158/0008-5472.can-14-2729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel D, Huang SM, Baglia LA, McCance DJ (1999) The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. EMBO J 18(18):5061–5072. doi:10.1093/emboj/18.18.5061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearson S, Jia H, Kandachi K (2004) China approves first gene therapy. Nat Biotechnol 22(1):3–4. doi:10.1038/nbt0104-3

    Article  CAS  PubMed  Google Scholar 

  • Perri F, Pacelli R, Della Vittoria Scarpati G, Cella L, Giuliano M, Caponigro F, Pepe S (2015) Radioresistance in head and neck squamous cell carcinoma: biological bases and therapeutic implications. Head Neck 37(5):763–770. doi:10.1002/hed.23837

    Article  PubMed  Google Scholar 

  • Perrone F, Bossi P, Cortelazzi B, Locati L, Quattrone P, Pierotti MA, Pilotti S, Licitra L (2010) TP53 mutations and pathologic complete response to neoadjuvant cisplatin and fluorouracil chemotherapy in resected oral cavity squamous cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 28(5):761–766. doi:10.1200/jco.2009.22.4170

    Article  CAS  Google Scholar 

  • Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, Ridge JA, Goodwin J, Kenady D, Saunders J, Westra W, Sidransky D, Koch WM (2007) TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 357(25):2552–2561. doi:10.1056/NEJMoa073770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rippin TM, Bykov VJ, Freund SM, Selivanova G, Wiman KG, Fersht AR (2002) Characterization of the p53-rescue drug CP-31398 in vitro and in living cells. Oncogene 21(14):2119–2129. doi:10.1038/sj.onc.1205362

    Article  CAS  PubMed  Google Scholar 

  • Roh JL, Kang SK, Minn I, Califano JA, Sidransky D, Koch WM (2011) p53-Reactivating small molecules induce apoptosis and enhance chemotherapeutic cytotoxicity in head and neck squamous cell carcinoma. Oral Oncol 47(1):8–15. doi:10.1016/j.oraloncology.2010.10.011

    Article  CAS  PubMed  Google Scholar 

  • Sankala H, Vaughan C, Wang J, Deb S, Graves PR (2011) Upregulation of the mitochondrial transport protein, Tim50, by mutant p53 contributes to cell growth and chemoresistance. Arch Biochem Biophys 512(1):52–60. doi:10.1016/j.abb.2011.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheffner M, Huibregtse JM, Vierstra RD, Howley PM (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75(3):495–505. doi:10.1016/0092-8674(93)90384-3

    Article  CAS  PubMed  Google Scholar 

  • Sigal A, Rotter V (2000) Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res 60(24):6788–6793

    CAS  PubMed  Google Scholar 

  • Skinner HD, Sandulache VC, Ow TJ, Meyn RE, Yordy JS, Beadle BM, Fitzgerald AL, Giri U, Ang KK, Myers JN (2012) TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. Clin Cancer Res Off J Am Assoc Cancer Res 18(1):290–300. doi:10.1158/1078-0432.ccr-11-2260

    Article  CAS  Google Scholar 

  • Smeets SJ, van der Plas M, Schaaij-Visser TB, van Veen EA, van Meerloo J, Braakhuis BJ, Steenbergen RD, Brakenhoff RH (2011) Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways. Int J Cancer 128(7):1596–1605. doi:10.1002/ijc.25474

    Article  CAS  PubMed  Google Scholar 

  • Song H, Hollstein M, Xu Y (2007) p 53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol 9(5):573–580. doi:http://www.nature.com/ncb/journal/v9/n5/suppinfo/ncb1571_S1.html

  • Strano S, Dell’Orso S, Di Agostino S, Fontemaggi G, Sacchi A, Blandino G (2007) Mutant p53: an oncogenic transcription factor. Oncogene 26(15):2212–2219

    Article  CAS  PubMed  Google Scholar 

  • Sturgis EM, Cinciripini PM (2007) Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer 110(7):1429–1435. doi:10.1002/cncr.22963

    Article  PubMed  Google Scholar 

  • Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K (2009) Modulation of microRNA processing by p53. Nature 460(7254):529–533. doi:10.1038/nature08199

    Article  CAS  PubMed  Google Scholar 

  • Szentkúti G, Dános K, Brauswetter D, Kiszner G, Krenács T, Csákó L, Répássy G, Tamás L (2015) Correlations between prognosis and regional biomarker profiles in head and neck squamous cell carcinomas. Pathol Oncol Res 21(3):643–650. doi:10.1007/s12253-014-9869-4

    Article  PubMed  Google Scholar 

  • Takimoto R, Wang W, Dicker DT, Rastinejad F, Lyssikatos J, el-Deiry WS (2002) The mutant p 53-conformation modifying drug, CP-31398, can induce apoptosis of human cancer cells and can stabilize wild-type p53 protein. Cancer Biol Ther 1(1):47–55

    Google Scholar 

  • Tandon S, Tudur-Smith C, Riley RD, Boyd MT, Jones TM (2010) A systematic review of p53 as a prognostic factor of survival in squamous cell carcinoma of the four main anatomical subsites of the head and neck. Cancer Epidemiol Biomarkers Prev 19(2):574–587. doi:10.1158/1055-9965.epi-09-0981 (A publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanner S, Barberis A (2004) CP-31398, a putative p53-stabilizing molecule tested in mammalian cells and in yeast for its effects on p53 transcriptional activity. J Negat Results Biomed 3:5. doi:10.1186/1477-5751-3-5

    Article  PubMed  PubMed Central  Google Scholar 

  • Tassone P, Old M, Teknos TN, Pan Q (2013) p53-based therapeutics for head and neck squamous cell carcinoma. Oral Oncol 49(8):733–737. doi:10.1016/j.oraloncology.2013.03.447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • The Cancer Genome Atlas N (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517(7536):576–582. doi:10.1038/nature14129. http://www.nature.com/nature/journal/v517/n7536/abs/nature14129.html-supplementary-information

  • Valenti F, Ganci F, Fontemaggi G, Sacconi A, Strano S, Blandino G, Di Agostino S (2015) Gain of function mutant p53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression. Oncotarget 6(8):5547–5566. doi:10.18632/oncotarget.2587

    Article  PubMed  PubMed Central  Google Scholar 

  • Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303(5659):844–848. doi:10.1126/science.1092472

    Article  CAS  PubMed  Google Scholar 

  • Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8(4):275–283. doi:10.1038/nrm2147

    Article  CAS  PubMed  Google Scholar 

  • Vousden KH, Lu X (2002) Live or let die: the cell’s response to p53. Nat Rev Cancer 2(8):594–604

    Article  CAS  PubMed  Google Scholar 

  • Wang YV, Leblanc M, Wade M, Jochemsen AG, Wahl GM (2009) Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA-damage-activated kinases. Cancer Cell 16(1):33–43. doi:10.1016/j.ccr.2009.05.008

    Article  PubMed  PubMed Central  Google Scholar 

  • Wichmann G, Rosolowski M, Krohn K, Kreuz M, Boehm A, Reiche A, Scharrer U, Halama D, Bertolini J, Bauer U, Holzinger D, Pawlita M, Hess J, Engel C, Hasenclever D, Scholz M, Ahnert P, Kirsten H, Hemprich A, Wittekind C, Herbarth O, Horn F, Dietz A, Loeffler M (2015) The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer. Int J Cancer 137(12):2846–2857. doi:10.1002/ijc.29649

    Article  CAS  PubMed  Google Scholar 

  • Wiest T, Schwarz E, Enders C, Flechtenmacher C, Bosch FX (2002) Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRB cell cycle control. Oncogene 21(10):1510–1517. doi:10.1038/sj/onc/1205214

    Article  CAS  PubMed  Google Scholar 

  • Xie X, Piao L, Bullock BN, Smith A, Su T, Zhang M, Teknos TN, Arora PS, Pan Q (2014) Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma. Oncogene 33(8):1037–1046. doi:10.1038/onc.2013.25

    Article  CAS  PubMed  Google Scholar 

  • Yoo GH, Piechocki MP, Oliver J, Lonardo F, Zumstein L, Lin HS, Kim H, Shibuya TY, Shehadeh N, Ensley JF (2004) Enhancement of Ad-p53 therapy with docetaxel in head and neck cancer. Laryngoscope 114(11):1871–1879. doi:10.1097/01.mlg.0000147914.51239.ed

    Article  CAS  PubMed  Google Scholar 

  • Yoo GH, Moon J, Leblanc M, Lonardo F, Urba S, Kim H, Hanna E, Tsue T, Valentino J, Ensley J, Wolf G (2009) A phase 2 trial of surgery with perioperative INGN 201 (Ad5CMV-p 53) gene therapy followed by chemoradiotherapy for advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx: report of the Southwest Oncology Group. Arch Otolaryngol Head Neck Surg 135(9):869–874. doi:10.1001/archoto.2009.122

  • Yu J, Zhang L (2003) No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell 4(4):248–249

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Xiong Y (2001) Control of p53 ubiquitination and nuclear export by MDM2 and ARF. Cell Growth Differ 12(4):175–186

    CAS  PubMed  Google Scholar 

  • Zhang S, Li Y, Li L, Zhang Y, Gao N, Zhang Z, Zhao H (2009) Phase i study of repeated intraepithelial delivery of adenoviral p53 in patients with dysplastic oral leukoplakia. J Oral Maxillofac Surg 67(5):1074–1082. doi:10.1016/j.joms.2008.06.079

    Article  PubMed  Google Scholar 

  • Zhao CY, Grinkevich VV, Nikulenkov F, Bao W, Selivanova G (2010) Rescue of the apoptotic-inducing function of mutant p 53 by small molecule RITA. Cell Cycle (Georgetown, Tex) 9(9):1847–1855. doi:10.4161/cc.9.9.11545

  • Zhou G, Liu Z, Myers JN (2016) TP53 mutations in head and neck squamous cell carcinoma and their impact on disease progression and treatment response. J Cell Biochem. doi:10.1002/jcb.25592

    Google Scholar 

  • Ziemann F, Arenz A, Preising S, Wittekindt C, Klussmann JP, Engenhart-Cabillic R, Wittig A (2015) Increased sensitivity of HPV-positive head and neck cancer cell lines to x-irradiation ± Cisplatin due to decreased expression of E6 and E7 oncoproteins and enhanced apoptosis. Am J Cancer Res 5(3):1017–1031

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Ohio State University College of Medicine, Columbus, OH, USA

    Ramez Philips

  2. Department of Otolaryngology, The Ohio State University Medical Center, Columbus, OH, USA

    Quintin Pan

Authors
  1. Ramez Philips
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Quintin Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ramez Philips .

Editor information

Editors and Affiliations

  1. Oral Medicine, King's College London Oral Medicine, Surrey, United Kingdom

    Saman Warnakulasuriya

  2. Cedars-Sinai Medical Center, Department of Biomedical Sciences Cedars-Sinai Medical Center, Los Angeles, California, USA

    Zakir Khan

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Philips, R., Pan, Q. (2017). p53 in Head and Neck Squamous Cell Carcinoma. In: Warnakulasuriya, S., Khan, Z. (eds) Squamous cell Carcinoma. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1084-6_5

Download citation

Publish with us

Policies and ethics

Search

Navigation