S100A2 in cancerogenesis: a friend or a foe?

Abstract

Owing to the exceptional intracellular distribution and the heterogeneous expression pattern during transformation and metastasis in various tumors, the EF-hand calcium-binding protein S100A2 attracts increasing attention. Unlike the majority of S100 proteins, S100A2 expression is downregulated in many cancers and the loss in nuclear expression has been associated with poor prognosis. On the other hand, S100A2 is upregulated in some cancers. This mini review highlights the general characteristics of S100A2 and discusses recent findings on its putative functional implication as a suppressor or promoter in cancerogenesis.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Almadori G et al (2009) Diminished expression of S100A2, a putative tumour suppressor, is an independent predictive factor of neck node relapse in laryngeal squamous cell carcinoma. J Otolaryngol Head Neck Surg 38:16–22

    PubMed  Google Scholar 

  2. Andersen LB, Xia L, Stoll S, Zhao X, Elder JT (1996) Lineage-specific CaN19 expression in human skin: lack of expression in normal melanocytes. J Dermatol Sci 12:69–72

    PubMed  Article  CAS  Google Scholar 

  3. Bartling B, Rehbein G, Schmitt WD, Hofmann HS, Silber RE, Simm A (2007) S100A2–S100P expression profile and diagnosis of non-small cell lung carcinoma: impairment by advanced tumour stages and neoadjuvant chemotherapy. Eur J Cancer 43:1935–1943

    PubMed  Article  CAS  Google Scholar 

  4. Biankin AV et al (2009) Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer. Gastroenterology 137:558–568, 568 e551–511

    Google Scholar 

  5. Boni R, Burg G, Doguoglu A, Ilg EC, Schafer BW, Muller B, Heizmann CW (1997) Immunohistochemical localization of the Ca2+ binding S100 proteins in normal human skin and melanocytic lesions. Br J Dermatol 137:39–43

    PubMed  Article  CAS  Google Scholar 

  6. Botelho HM, Koch M, Fritz G, Gomes CM (2009) Metal ions modulate the folding and stability of the tumor suppressor protein S100A2. FEBS J 276:1776–1786

    PubMed  Article  CAS  Google Scholar 

  7. Bulk E et al (2009) S100A2 induces metastasis in non-small cell lung cancer. Clin Cancer Res 15:22–29

    PubMed  Article  CAS  Google Scholar 

  8. Cao LY, Yin Y, Li H, Jiang Y, Zhang HF (2009) Expression and clinical significance of S100A2 and p63 in esophageal carcinoma. World J Gastroenterol 15:4183–4188

    PubMed  Article  CAS  Google Scholar 

  9. Chen Z, Zhang K, Zhang X, Yuan XH, Yuan Z, Jin L, Xiong M (2003) Comparison of gene expression between metastatic derivatives and their poorly metastatic parental cells implicates crucial tumor-environment interaction in metastasis of head and neck squamous cell carcinoma. Clin Exp Metastasis 20:335–342

    PubMed  Article  CAS  Google Scholar 

  10. Craig RW, Jabs EW, Zhou P, Kozopas KM, Hawkins AL, Rochelle JM, Seldin MF, Griffin CA (1994) Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease. Genomics 23:457–463

    PubMed  Article  CAS  Google Scholar 

  11. Deshpande R, Woods TL, Fu J, Zhang T, Stoll SW, Elder JT (2000) Biochemical characterization of S100A2 in human keratinocytes: subcellular localization, dimerization, and oxidative cross-linking. J Invest Dermatol 115:477–485

    PubMed  Article  CAS  Google Scholar 

  12. Diederichs S et al (2004) S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 64:5564–5569

    PubMed  Article  CAS  Google Scholar 

  13. Donato R (2003) Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 60:540–551

    PubMed  Article  CAS  Google Scholar 

  14. Eckert RL, Broome AM, Ruse M, Robinson N, Ryan D, Lee K (2004) S100 proteins in the epidermis. J Invest Dermatol 123:23–33

    PubMed  Article  CAS  Google Scholar 

  15. Elder JT, Zhao X (2002) Evidence for local control of gene expression in the epidermal differentiation complex. Exp Dermatol 11:406–412

    PubMed  Article  CAS  Google Scholar 

  16. El-Rifai W, Moskaluk CA, Abdrabbo MK, Harper J, Yoshida C, Riggins GJ, Frierson HF Jr, Powell SM (2002) Gastric cancers overexpress S100A calcium-binding proteins. Cancer Res 62:6823–6826

    PubMed  CAS  Google Scholar 

  17. Engelkamp D, Schafer BW, Mattei MG, Erne P, Heizmann CW (1993) Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. Proc Natl Acad Sci USA 90:6547–6551

    PubMed  Article  CAS  Google Scholar 

  18. Feng G, Xu X, Youssef EM, Lotan R (2001) Diminished expression of S100A2, a putative tumor suppressor, at early stage of human lung carcinogenesis. Cancer Res 61:7999–8004

    PubMed  CAS  Google Scholar 

  19. Fernandez-Fernandez MR, Rutherford TJ, Fersht AR (2008) Members of the S100 family bind p53 in two distinct ways. Protein Sci 17:1663–1670

    PubMed  Article  CAS  Google Scholar 

  20. Foser S, Redwanz I, Ebeling M, Heizmann CW, Certa U (2006) Interferon-alpha and transforming growth factor-beta co-induce growth inhibition of human tumor cells. Cell Mol Life Sci 63:2387–2396

    PubMed  Article  CAS  Google Scholar 

  21. Franz C, Durussel I, Cox JA, Schafer BW, Heizmann CW (1998) Binding of Ca2+ and Zn2+ to human nuclear S100A2 and mutant proteins. J Biol Chem 273:18826–18834

    PubMed  Article  CAS  Google Scholar 

  22. Gimona M, Lando Z, Dolginov Y, Vandekerckhove J, Kobayashi R, Sobieszek A, Helfman DM (1997) Ca2+-dependent interaction of S100A2 with muscle and nonmuscle tropomyosins. J Cell Sci 110(Pt 5):611–621

    PubMed  CAS  Google Scholar 

  23. Glenney JR Jr, Kindy MS, Zokas L (1989) Isolation of a new member of the S100 protein family: amino acid sequence, tissue, and subcellular distribution. J Cell Biol 108:569–578

    PubMed  Article  CAS  Google Scholar 

  24. Gollob JA, Sciambi CJ (2007) Decitabine up-regulates S100A2 expression and synergizes with IFN-gamma to kill uveal melanoma cells. Clin Cancer Res 13:5219–5225

    PubMed  Article  CAS  Google Scholar 

  25. Gupta S, Hussain T, MacLennan GT, Fu P, Patel J, Mukhtar H (2003) Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma. J Clin Oncol 21:106–112

    PubMed  Article  CAS  Google Scholar 

  26. Heighway J et al (2002) Expression profiling of primary non-small cell lung cancer for target identification. Oncogene 21:7749–7763

    PubMed  Article  CAS  Google Scholar 

  27. Heizmann CW, Cox JA (1998) New perspectives on S100 proteins: a multi-functional Ca(2+)-, Zn(2+)- and Cu(2+)-binding protein family. Biometals 11:383–397

    PubMed  Article  CAS  Google Scholar 

  28. Hibi K, Fujitake S, Takase T, Kodera Y, Ito K, Akiyama S, Shirane M, Nakao A (2003) Identification of S100A2 as a target of the DeltaNp63 oncogenic pathway. Clin Cancer Res 9:4282–4285

    PubMed  CAS  Google Scholar 

  29. Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ (2001) Coordinately up-regulated genes in ovarian cancer. Cancer Res 61:3869–3876

    PubMed  CAS  Google Scholar 

  30. Huang JW, Ming Z, Shrestha P, Mori M, Ilg E, Schafer BW, Heizmann CW (1996) Immunohistochemical evaluation of the Ca(2+)-binding S-100 proteins S-100A1, S-100A2, S-100A4, S-100A6 and S-100B in salivary gland tumors. J Oral Pathol Med 25:547–555

    PubMed  Article  CAS  Google Scholar 

  31. Ilg EC, Schafer BW, Heizmann CW (1996) Expression pattern of S100 calcium-binding proteins in human tumors. Int J Cancer 68:325–332

    PubMed  Article  CAS  Google Scholar 

  32. Imazawa M, Hibi K, Fujitake S, Kodera Y, Ito K, Akiyama S, Nakao A (2005) S100A2 overexpression is frequently observed in esophageal squamous cell carcinoma. Anticancer Res 25:1247–1250

    PubMed  CAS  Google Scholar 

  33. Ito Y, Yoshida H, Tomoda C, Uruno T, Miya A, Kobayashi K, Matsuzuka F, Kakudo K, Kuma K, Miyauchi A (2005) Expression of S100A2 and S100A6 in thyroid carcinomas. Histopathology 46:569–575

    PubMed  Article  CAS  Google Scholar 

  34. Jeronimo C, Henrique R, Hoque MO, Mambo E, Ribeiro FR, Varzim G, Oliveira J, Teixeira MR, Lopes C, Sidransky D (2004) A quantitative promoter methylation profile of prostate cancer. Clin Cancer Res 10:8472–8478

    PubMed  Article  CAS  Google Scholar 

  35. Ji J, Zhao L, Wang X, Zhou C, Ding F, Su L, Zhang C, Mao X, Wu M, Liu Z (2004) Differential expression of S100 gene family in human esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 130:480–486

    PubMed  Article  CAS  Google Scholar 

  36. Kirschner RD, Sanger K, Muller GA, Engeland K (2008) Transcriptional activation of the tumor suppressor and differentiation gene S100A2 by a novel p63-binding site. Nucleic Acids Res 36:2969–2980

    PubMed  Article  CAS  Google Scholar 

  37. Klopper JP, Sharma V, Bissonnette R, Haugen BR (2010) Combination PPARgamma and RXR agonist treatment in melanoma cells: functional importance of S100A2. PPAR Res 2010:729876

    PubMed  Article  Google Scholar 

  38. Koch M, Diez J, Fritz G (2006) Purification and crystallization of the human EF-hand tumour suppressor protein S100A2. Acta Crystallogr Sect F Struct Biol Cryst Commun 62:1120–1123

    PubMed  Article  Google Scholar 

  39. Koch M, Bhattacharya S, Kehl T, Gimona M, Vasak M, Chazin W, Heizmann CW, Kroneck PM, Fritz G (2007) Implications on zinc binding to S100A2. Biochim Biophys Acta 1773:457–470

    PubMed  Article  CAS  Google Scholar 

  40. Koch M, Diez J, Fritz G (2008) Crystal structure of Ca2+-free S100A2 at 1.6-A resolution. J Mol Biol 378:933–942

    PubMed  Article  Google Scholar 

  41. Komada T, Araki R, Nakatani K, Yada I, Naka M, Tanaka T (1996) Novel specific chemtactic receptor for S100L protein on guinea pig eosinophils. Biochem Biophys Res Commun 220:871–874

    PubMed  Article  CAS  Google Scholar 

  42. Kyriazanos ID, Tachibana M, Dhar DK, Shibakita M, Ono T, Kohno H, Nagasue N (2002) Expression and prognostic significance of S100A2 protein in squamous cell carcinoma of the esophagus. Oncol Rep 9:503–510

    PubMed  CAS  Google Scholar 

  43. Lapi E, Iovino A, Fontemaggi G, Soliera AR, Iacovelli S, Sacchi A, Rechavi G, Givol D, Blandino G, Strano S (2006) S100A2 gene is a direct transcriptional target of p53 homologues during keratinocyte differentiation. Oncogene 25:3628–3637

    PubMed  Article  CAS  Google Scholar 

  44. Lauriola L, Michetti F, Maggiano N, Galli J, Cadoni G, Schafer BW, Heizmann CW, Ranelletti FO (2000) Prognostic significance of the Ca(2+) binding protein S100A2 in laryngeal squamous-cell carcinoma. Int J Cancer 89:345–349

    PubMed  Article  CAS  Google Scholar 

  45. Leclerc E, Fritz G, Vetter SW, Heizmann CW (2008) Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta 1793:993–1007

    PubMed  Article  Google Scholar 

  46. Lee SW, Tomasetto C, Sager R (1991) Positive selection of candidate tumor-suppressor genes by subtractive hybridization. Proc Natl Acad Sci USA 88:2825–2829

    PubMed  Article  CAS  Google Scholar 

  47. Lee SW, Tomasetto C, Swisshelm K, Keyomarsi K, Sager R (1992) Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment. Proc Natl Acad Sci USA 89:2504–2508

    PubMed  Article  CAS  Google Scholar 

  48. Lee OJ, Hong SM, Razvi MH, Peng D, Powell SM, Smoklin M, Moskaluk CA, El-Rifai W (2006) Expression of calcium-binding proteins S100A2 and S100A4 in Barrett’s adenocarcinomas. Neoplasia 8:843–850

    PubMed  Article  CAS  Google Scholar 

  49. Li Y, Gudjonsson JE, Woods TL, Zhang T, Johnston A, Stoll SW, Elder JT (2009) Transgenic expression of S100A2 in hairless mouse skin enhances Cxcl13 mRNA in response to solar-simulated radiation. Arch Dermatol Res 301:205–217

    PubMed  Article  CAS  Google Scholar 

  50. Liu D, Rudland PS, Sibson DR, Platt-Higgins A, Barraclough R (2000) Expression of calcium-binding protein S100A2 in breast lesions. Br J Cancer 83:1473–1479

    PubMed  Article  CAS  Google Scholar 

  51. Liu J, Li X, Dong GL, Zhang HW, Chen DL, Du JJ, Zheng JY, Li JP, Wang WZ (2008) In silico analysis and verification of S100 gene expression in gastric cancer. BMC Cancer 8:261

    PubMed  Article  Google Scholar 

  52. Maelandsmo GM, Florenes VA, Mellingsaeter T, Hovig E, Kerbel RS, Fodstad O (1997) Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. Int J Cancer 74:464–469

    PubMed  Article  CAS  Google Scholar 

  53. Mandinova A, Atar D, Schafer BW, Spiess M, Aebi U, Heizmann CW (1998) Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises in intracellular calcium. J Cell Sci 111(Pt 14):2043–2054

    PubMed  CAS  Google Scholar 

  54. Marenholz I, Heizmann CW, Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 322:1111–1122

    PubMed  Article  CAS  Google Scholar 

  55. Matsubara D et al (2005) Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes. Cancer Sci 96:844–857

    PubMed  Article  CAS  Google Scholar 

  56. Matsumoto K, Irie A, Satoh T, Ishii J, Iwabuchi K, Iwamura M, Egawa S, Baba S (2007) Expression of S100A2 and S100A4 predicts for disease progression and patient survival in bladder cancer. Urology 70:602–607

    PubMed  Article  Google Scholar 

  57. Mueller A, Bachi T, Hochli M, Schafer BW, Heizmann CW (1999) Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation. Histochem Cell Biol 111:453–459

    PubMed  Article  CAS  Google Scholar 

  58. Mueller A, Schafer BW, Ferrari S, Weibel M, Makek M, Hochli M, Heizmann CW (2005) The calcium-binding protein S100A2 interacts with p53 and modulates its transcriptional activity. J Biol Chem 280:29186–29193

    PubMed  Article  CAS  Google Scholar 

  59. Nagy N et al (2001) S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell carcinoma migration. Lab Invest 81:599–612

    PubMed  CAS  Google Scholar 

  60. Nagy N, Hoyaux D, Gielen I, Schafer BW, Pochet R, Heizmann CW, Kiss R, Salmon I, Decaestecker C (2002) The Ca2+-binding S100A2 protein is differentially expressed in epithelial tissue of glandular or squamous origin. Histol Histopathol 17:123–130

    PubMed  CAS  Google Scholar 

  61. Nonaka D, Chiriboga L, Rubin BP (2008) Differential expression of S100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J Cutan Pathol 35:1014–1019

    PubMed  Article  Google Scholar 

  62. Ohuchida K, Mizumoto K, Ishikawa N, Fujii K, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M (2005) The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clin Cancer Res 11:7785–7793

    PubMed  Article  CAS  Google Scholar 

  63. Ohuchida K et al (2007) Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis. J Pathol 213:275–282

    PubMed  Article  CAS  Google Scholar 

  64. Pedrocchi M, Schafer BW, Mueller H, Eppenberger U, Heizmann CW (1994) Expression of Ca(2+)-binding proteins of the S100 family in malignant human breast-cancer cell lines and biopsy samples. Int J Cancer 57:684–690

    PubMed  Article  CAS  Google Scholar 

  65. Randazzo A, Acklin C, Schafer BW, Heizmann CW, Chazin WJ (2001) Structural insight into human Zn(2+)-bound S100A2 from NMR and homology modeling. Biochem Biophys Res Commun 288:462–467

    PubMed  Article  CAS  Google Scholar 

  66. Ravasi T, Hsu K, Goyette J, Schroder K, Yang Z, Rahimi F, Miranda LP, Alewood PF, Hume DA, Geczy C (2004) Probing the S100 protein family through genomic and functional analysis. Genomics 84:10–22

    PubMed  Article  CAS  Google Scholar 

  67. Rehman I, Cross SS, Catto JW, Leiblich A, Mukherjee A, Azzouzi AR, Leung HY, Hamdy FC (2005) Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer. Prostate 65:322–330

    PubMed  Article  CAS  Google Scholar 

  68. Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS (2006) Calcium-dependent and -independent interactions of the S100 protein family. Biochem J 396:201–214

    PubMed  Article  CAS  Google Scholar 

  69. Shimamoto S, Takata M, Tokuda M, Oohira F, Tokumitsu H, Kobayashi R (2008) Interactions of S100A2 and S100A6 with the tetratricopeptide repeat proteins, Hsp90/Hsp70-organizing protein and kinesin light chain. J Biol Chem 283:28246–28258

    PubMed  Article  CAS  Google Scholar 

  70. Shrestha P, Muramatsu Y, Kudeken W, Mori M, Takai Y, Ilg EC, Schafer BW, Heizmann CW (1998) Localization of Ca(2+)-binding S100 proteins in epithelial tumours of the skin. Virchows Arch 432:53–59

    PubMed  Article  CAS  Google Scholar 

  71. Smith SL, Gugger M, Hoban P, Ratschiller D, Watson SG, Field JK, Betticher DC, Heighway J (2004) S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial lesions and primary non-small cell lung carcinomas. Br J Cancer 91:1515–1524

    PubMed  CAS  Google Scholar 

  72. Stoll SW, Zhao X, Elder JT (1998) EGF stimulates transcription of CaN19 (S100A2) in HaCaT keratinocytes. J Invest Dermatol 111:1092–1097

    PubMed  Article  CAS  Google Scholar 

  73. Stoll SW, Chia NV, Nair RP, Woods TL, Stuart P, Henseler T, Jenisch S, Christophers E, Voorhees JJ, Elder JT (2001) S100A2 coding sequence polymorphism: characterization and lack of association with psoriasis. Clin Exp Dermatol 26:79–83

    PubMed  Article  CAS  Google Scholar 

  74. Stradal TB, Troxler H, Heizmann CW, Gimona M (2000) Mapping the zinc ligands of S100A2 by site-directed mutagenesis. J Biol Chem 275:13219–13227

    PubMed  Article  CAS  Google Scholar 

  75. Strazisar M, Rott T, Glavac D (2009a) Frequent polymorphic variations but rare tumour specific mutations of the S100A2 on 1q21 in non-small cell lung cancer. Lung Cancer 63:354–359

    PubMed  Article  Google Scholar 

  76. Strazisar M, Mlakar V, Glavac D (2009b) The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC). Cell Mol Biol Lett 14:442–456

    PubMed  Article  CAS  Google Scholar 

  77. Suzuki F, Oridate N, Homma A, Nakamaru Y, Nagahashi T, Yagi K, Yamaguchi S, Furuta Y, Fukuda S (2005) S100A2 expression as a predictive marker for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral cavity. Oncol Rep 14:1493–1498

    PubMed  CAS  Google Scholar 

  78. Tan M, Heizmann CW, Guan K, Schafer BW, Sun Y (1999) Transcriptional activation of the human S100A2 promoter by wild-type p53. FEBS Lett 445:265–268

    PubMed  Article  CAS  Google Scholar 

  79. Tsai ST, Jin YT, Tsai WC, Wang ST, Lin YC, Chang MT, Wu LW (2005) S100A2, a potential marker for early recurrence in early-stage oral cancer. Oral Oncol 41:349–357

    PubMed  Article  CAS  Google Scholar 

  80. Tsai WC, Tsai ST, Jin YT, Wu LW (2006) Cyclooxygenase-2 is involved in S100A2-mediated tumor suppression in squamous cell carcinoma. Mol Cancer Res 4:539–547

    PubMed  Article  CAS  Google Scholar 

  81. van Dieck J, Fernandez-Fernandez MR, Veprintsev DB, Fersht AR (2009a) Modulation of the oligomerization state of p53 by differential binding of proteins of the S100family to p53 monomers and tetramers. J Biol Chem 284:13804–13811

    PubMed  Article  Google Scholar 

  82. van Dieck J, Teufel DP, Jaulent AM, Fernandez-Fernandez MR, Rutherford TJ, Wyslouch-Cieszynska A, Fersht AR (2009b) Posttranslational modifications affect the interaction of S100 proteins with tumor suppressor p53. J Mol Biol 394:922–930

    PubMed  Article  Google Scholar 

  83. van Dieck J, Brandt T, Teufel DP, Veprintsev DB, Joerger AC, Fersht AR (2010) Molecular basis of S100 proteins interacting with the p53 homologs p63 and p73. Oncogene 29:2024–2035

    PubMed  Article  Google Scholar 

  84. Villaret DB, Wang T, Dillon D, Xu J, Sivam D, Cheever MA, Reed SG (2000) Identification of genes overexpressed in head and neck squamous cell carcinoma using a combination of complementary DNA subtraction and microarray analysis. Laryngoscope 110:374–381

    PubMed  Article  CAS  Google Scholar 

  85. Wang H, Zhang Z, Li R, Ang KK, Zhang H, Caraway NP, Katz RL, Jiang F (2005) Overexpression of S100A2 protein as a prognostic marker for patients with stage I non small cell lung cancer. Int J Cancer 116:285–290

    PubMed  Article  CAS  Google Scholar 

  86. Wicki R, Franz C, Scholl FA, Heizmann CW, Schafer BW (1997) Repression of the candidate tumor suppressor gene S100A2 in breast cancer is mediated by site-specific hypermethylation. Cell Calcium 22:243–254

    PubMed  Article  CAS  Google Scholar 

  87. Xia L, Stoll SW, Liebert M, Ethier SP, Carey T, Esclamado R, Carroll W, Johnson TM, Elder JT (1997) CaN19 expression in benign and malignant hyperplasias of the skin and oral mucosa: evidence for a role in regenerative differentiation. Cancer Res 57:3055–3062

    PubMed  CAS  Google Scholar 

  88. Yang A, Kaghad M, Caput D, McKeon F (2002) On the shoulders of giants: p63, p73 and the rise of p53. Trends Genet 18:90–95

    PubMed  Article  Google Scholar 

  89. Zech VF, Dlaska M, Tzankov A, Hilbe W (2006) Prognostic and diagnostic relevance of hnRNP A2/B1, hnRNP B1 and S100 A2 in non-small cell lung cancer. Cancer Detect Prev 30:395–402

    PubMed  Article  CAS  Google Scholar 

  90. Zhang T, Woods TL, Elder JT (2002) Differential responses of S100A2 to oxidative stress and increased intracellular calcium in normal, immortalized, and malignant human keratinocytes. J Invest Dermatol 119:1196–1201

    PubMed  Article  CAS  Google Scholar 

  91. Zhang X, Hunt JL, Shin DM, Chen ZG (2007) Down-regulation of S100A2 in lymph node metastases of head and neck cancer. Head Neck 29:236–243

    PubMed  Article  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from Deutsche Forschungsgemeinschaft (DFG, grant No. PI 304/1-1).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jens Pietzsch.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wolf, S., Haase-Kohn, C. & Pietzsch, J. S100A2 in cancerogenesis: a friend or a foe?. Amino Acids 41, 849–861 (2011). https://doi.org/10.1007/s00726-010-0623-2

Download citation

Keywords

  • Calcium-binding protein
  • EF-hand
  • p53 Protein family
  • Receptor for advanced glycation endproducts (RAGE)
  • Tumor promotor
  • Tumor suppressor