P-cadherin and the journey to cancer metastasis

Molecular Cancer

Volumn 14, Issue 1, 2015, Pages

  Vieira, André Filipe ^a,b   Paredes, Joana ^a,b,c  

^a UNIVERSITY OF PORTO   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

^c University of Porto   (Portugal)

Author keywords

Cancer; Cancer stem cells; Invasion; Metastasis; P cadherin

Indexed keywords

GELATINASE A; GLYCOGEN SYNTHASE KINASE 3BETA; INTERSTITIAL COLLAGENASE; P CADHERIN; TRANSCRIPTION FACTOR SNAIL; CADHERIN;

CANCER INHIBITION; CANCER PROGNOSIS; CANCER SURVIVAL; CARCINOGENESIS; CELL ACTIVATION; CELL CONTACT; CELL MIGRATION; CELL PROLIFERATION; DISEASE ASSOCIATION; DISTANT METASTASIS; DOWN REGULATION; ENZYME ACTIVATION; ENZYME INACTIVATION; ENZYME RELEASE; HUMAN; NONHUMAN; OVERALL SURVIVAL; PROGRESSION FREE SURVIVAL; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; REGIONAL METASTASIS; REVIEW; SIGNAL TRANSDUCTION; TUMOR INVASION; TUMOR PROMOTION; UPREGULATION; CANCER STEM CELL; CELL TRANSFORMATION; GENETICS; METABOLISM; PATHOLOGY; PHYSIOLOGY;

CADHERINS; CELL TRANSFORMATION, NEOPLASTIC; HUMANS; NEOPLASM INVASIVENESS; NEOPLASTIC STEM CELLS; SIGNAL TRANSDUCTION;

EID: 84943426968     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/s12943-015-0448-4     Document Type: Review

References (111)

1. Nose A, Takeichi M. A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos. J Cell Biol. 1986;103(6 Pt 2):2649-58.
2. Hirai Y, Nose A, Kobayashi S, Takeichi M. Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis. Development. 1989;105(2):271-7.
3. Cavallaro U, Dejana E. Adhesion molecule signalling: not always a sticky business. Nat Rev Mol Cell Biol. 2011;12(3):189-97.
4. Larue L, Antos C, Butz S, Huber O, Delmas V, Dominis M, et al. A role for cadherins in tissue formation. Development. 1996;122(10):3185-94.
5. Raymond K, Deugnier MA, Faraldo MM, Glukhova MA. Adhesion within the stem cell niches. Curr Opin Cell Biol. 2009;21(5):623-9. doi: 10.1016/j.ceb.2009.05.004.
6. Albergaria A, Ribeiro AS, Vieira AF, Sousa B, Nobre AR, Seruca R, et al. P-cadherin role in normal breast development and cancer. Int J Dev Biol. 2011;55(7-8-9):811-22.
7. Hulpiau P, van Roy F. Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol. 2009;41(2):349-69.
8. Sahin H, Akpak YK, Berber U, Gun I, Demirel D, Ergur AR. Expression of P-cadherin (cadherin-3) and E-selectin in the villous trophoblast of first trimester human placenta. J Turk Ger Gynecol Assoc. 2014;15(1):13-7. doi: 10.5152/jtgga.2014.56563.
9. Imai K, Hirata S, Irie A, Senju S, Ikuta Y, Yokomine K, et al. Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers. Clin Cancer Res. 2008;14(20):6487-95.
10. Pizarro A, Gamallo C, Benito N, Palacios J, Quintanilla M, Cano A, et al. Differential patterns of placental and epithelial cadherin expression in basal cell carcinoma and in the epidermis overlying tumours. Br J Cancer. 1995;72(2):327-32.
11. Fujita M, Furukawa F, Fujii K, Horiguchi Y, Takeichi M, Imamura S. Expression of cadherin cell adhesion molecules during human skin development: morphogenesis of epidermis, hair follicles and eccrine sweat ducts. Arch Dermatol Res. 1992;284(3):159-66.
12. Kolle G, Ho M, Zhou Q, Chy HS, Krishnan K, Cloonan N, et al. Identification of human embryonic stem cell surface markers by combined membrane-polysome translation state array analysis and immunotranscriptional profiling. Stem cells (Dayton, Ohio). 2009;27(10):2446-56.
13. Rhee H, Polak L, Fuchs E. Lhx2 maintains stem cell character in hair follicles. Science. 2006;312(5782):1946-9.
14. Nassour M, Idoux-Gillet Y, Selmi A, Come C, Faraldo ML, Deugnier MA, et al. Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis. PLoS One. 2012;7(12):e53498. doi: 10.1371/journal.pone.0053498.
15. Paredes J, Milanezi F, Reis-Filho JS, Leitao D, Athanazio D, Schmitt F. Aberrant P-cadherin expression: is it associated with estrogen-independent growth in breast cancer? Pathol Res Pract. 2002;198(12):795-801.
16. Vieira AF, Ribeiro AS, Dionisio MR, Sousa B, Nobre AR, Albergaria A, et al. P-cadherin signals through the laminin receptor alpha6beta4 integrin to induce stem cell and invasive properties in basal-like breast cancer cells. Oncotarget. 2014.
17. Vieira AF, Ricardo S, Ablett MP, Dionisio MR, Mendes N, Albergaria A, et al. P-Cadherin is Co-Expressed with Cd44 and Cd49f and Mediates Stem Cell Properties in Basal-Like Breast Cancer. Stem cells (Dayton, Ohio). 2012;30(5):854-64. doi: 10.1002/stem.1075.
18. Daniel CW, Strickland P, Friedmann Y. Expression and functional role of E- and P-cadherins in mouse mammary ductal morphogenesis and growth. Dev Biol. 1995;169(2):511-9. doi: 10.1006/dbio.1995.1165.
19. Knudsen KA, Wheelock MJ. Cadherins and the mammary gland. J Cell Biochem. 2005;95(3):488-96. doi: 10.1002/jcb.20419.
20. Soler AP, Russo J, Russo IH, Knudsen KA. Soluble fragment of P-cadherin adhesion protein found in human milk. J Cell Biochem. 2002;85(1):180-4. doi: 10.1002/jcb.10126[pii].
21. Radice GL, Ferreira-Cornwell MC, Robinson SD, Rayburn H, Chodosh LA, Takeichi M, et al. Precocious mammary gland development in P-cadherin-deficient mice. J Cell Biol. 1997;139(4):1025-32.
22. Kendrick H, Regan JL, Magnay FA, Grigoriadis A, Mitsopoulos C, Zvelebil M, et al. Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate. BMC Genomics. 2008;9:591. doi: 10.1186/1471-2164-9-591.
23. Chanson L, Brownfield D, Garbe JC, Kuhn I, Stampfer MR, Bissell MJ, et al. Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells. Proc Natl Acad Sci U S A. 2011;108(8):3264-9. doi: 10.1073/pnas.1019556108.
24. Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS, Hines WC, et al. ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc Natl Acad Sci U S A. 2012;109(39):E2595-604. doi: 10.1073/pnas.1212834109.
25. Furukawa F, Fujii K, Horiguchi Y, Matsuyoshi N, Fujita M, Toda K, et al. Roles of E- and P-cadherin in the human skin. Microsc Res Tech. 1997;38(4):343-52. doi: 10.1002/(SICI)1097-0029(19970815)38:4<343::AID-JEMT2>3.0.CO;2-K.
26. Avitan-Hersh E, Indelman M, Khamaysi Z, Leibu R, Bergman R. A novel nonsense CDH3 mutation in hypotrichosis with juvenile macular dystrophy. Int J Dermatol. 2012;51(3):325-7. doi: 10.1111/j.1365-4632.2011.04973.x.
27. Sprecher E, Bergman R, Richard G, Lurie R, Shalev S, Petronius D, et al. Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin. Nat Genet. 2001;29(2):134-6. doi: 10.1038/ng716.
28. Halford S, Holt R, Nemeth AH, Downes SM. Homozygous deletion in CDH3 and hypotrichosis with juvenile macular dystrophy. Arch Ophthalmol. 2012;130(11):1490-2. doi: 10.1001/archophthalmol.2012.708.
29. Kjaer KW, Hansen L, Schwabe GC, Marques-de-Faria AP, Eiberg H, Mundlos S, et al. Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). J Med Genet. 2005;42(4):292-8. doi: 10.1136/jmg.2004.027821.
30. Basel-Vanagaite L, Pasmanik-Chor M, Lurie R, Yeheskel A, Kjaer KW. CDH3-Related Syndromes: Report on a New Mutation and Overview of the Genotype-Phenotype Correlations. Mol Syndromol. 2010;1(5):223-30. doi: 10.1159/000327156.
31. Indelman M, Eason J, Hummel M, Loza O, Suri M, Leys MJ, et al. Novel CDH3 mutations in hypotrichosis with juvenile macular dystrophy. Clin Exp Dermatol. 2007;32(2):191-6.
32. Indelman M, Hamel CP, Bergman R, Nischal KK, Thompson D, Surget MO, et al. Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular dystrophy. J Invest Dermatol. 2003;121(5):1217-20. doi: 10.1046/j.1523-1747.2003.12550_1.x.
33. Indelman M, Bergman R, Lurie R, Richard G, Miller B, Petronius D, et al. A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy. J Invest Dermatol. 2002;119(5):1210-3. doi: 10.1046/j.1523-1747.2002.19528.x.
34. Indelman M, Leibu R, Jammal A, Bergman R, Sprecher E. Molecular basis of hypotrichosis with juvenile macular dystrophy in two siblings. Br J Dermatol. 2005;153(3):635-8. doi: 10.1111/j.1365-2133.2005.06734.x.
35. Jelani M, Salman Chishti M, Ahmad W. A novel splice-site mutation in the CDH3 gene in hypotrichosis with juvenile macular dystrophy. Clin Exp Dermatol. 2009;34(1):68-73. doi: 10.1111/j.1365-2230.2008.02933.x.
36. Kamran-ul-Hassan Naqvi S, Azeem Z, Ali G, Ahmad W. A novel splice-acceptor site mutation in CDH3 gene in a consanguineous family exhibiting hypotrichosis with juvenile macular dystrophy. Arch Dermatol Res. 2010;302(9):701-3. doi: 10.1007/s00403-010-1035-6.
37. Shimomura Y, Wajid M, Kurban M, Christiano AM. Splice site mutations in the P-cadherin gene underlie hypotrichosis with juvenile macular dystrophy. Dermatology. 2010;220(3):208-12. doi: 10.1159/000275673.
38. Mandeville JA, Silva Neto B, Vanni AJ, Smith GL, Rieger-Christ KM, Zeheb R, et al. P-cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells. BJU Int. 2008;102(11):1707-14. doi: 10.1111/j.1464-410X.2008.08115.x.
39. Van Marck V, Stove C, Jacobs K, Van den Eynden G, Bracke M. P-cadherin in adhesion and invasion: opposite roles in colon and bladder carcinoma. Int J Cancer. 2011;128(5):1031-44.
40. Jarrard DF, Paul R, van Bokhoven A, Nguyen SH, Bova GS, Wheelock MJ, et al. P-Cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer. Clin Cancer Res. 1997;3(11):2121-8.
41. Wang P, Lin SL, Zhang LH, Li Z, Liu Q, Gao JX, et al. The prognostic value of P-cadherin in non-muscle-invasive bladder cancer. Eur J Surg Oncol. 2014;40(3):255-9. doi: 10.1016/j.ejso.2013.12.018.
42. Arenas MI, Romo E, Royuela M, Fraile B, Paniagua R. E-, N- and P-cadherin, and alpha-, beta- and gamma-catenin protein expression in normal, hyperplastic and carcinomatous human prostate. Histochem J. 2000;32(11):659-67.
43. Van Marck V, Stove C, Van Den Bossche K, Stove V, Paredes J, Vander Haeghen Y, et al. P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma. Cancer Res. 2005;65(19):8774-83. doi: 10.1158/0008-5472.CAN-04-4414.
44. Jacobs K, Feys L, Vanhoecke B, Van Marck V, Bracke M. P-cadherin expression reduces melanoma growth, invasion, and responsiveness to growth factors in nude mice. Eur J Cancer Prev. 2011;20(3):207-16. doi: 10.1097/CEJ.0b013e3283429e8b.
45. Smythe WR, Williams JP, Wheelock MJ, Johnson KR, Kaiser LR, Albelda SM. Cadherin and catenin expression in normal human bronchial epithelium and non-small cell lung cancer. Lung Cancer. 1999;24(3):157-68.
46. Foty RA, Steinberg MS. Measurement of tumor cell cohesion and suppression of invasion by E- or P-cadherin. Cancer Res. 1997;57(22):5033-6.
47. Lo Muzio L, Pannone G, Mignogna MD, Staibano S, Mariggio MA, Rubini C, et al. P-cadherin expression predicts clinical outcome in oral squamous cell carcinomas. Histol Histopathol. 2004;19(4):1089-99.
48. Munoz-Guerra MF, Marazuela EG, Fernandez-Contreras ME, Gamallo C. P-cadherin expression reduced in squamous cell carcinoma of the oral cavity: an indicatior of poor prognosis. Cancer. 2005;103(5):960-9. doi: 10.1002/cncr.20858.
49. Bauer K, Gosau M, Reinders J, Oefner P, Reichert TE, Bauer R. Presenilin 1/gamma-secretase modulates P-cadherin processing and influences cell adhesion in oral squamous cell carcinoma cell lines. Carcinogenesis. 2013;34(11):2622-8. doi: 10.1093/carcin/bgt211.
50. Bauer K, Dowejko A, Bosserhoff AK, Reichert TE, Bauer R. Slit-2 facilitates interaction of P-cadherin with Robo-3 and inhibits cell migration in an oral squamous cell carcinoma cell line. Carcinogenesis. 2011;32(6):935-43. doi: 10.1093/carcin/bgr059.
51. Bauer K, Dowejko A, Bosserhoff AK, Reichert TE, Bauer RJ. P-cadherin induces an epithelial-like phenotype in oral squamous cell carcinoma by GSK-3beta-mediated Snail phosphorylation. Carcinogenesis. 2009;30(10):1781-8. doi: 10.1093/carcin/bgp175.
52. Bauer R, Valletta D, Bauer K, Thasler WE, Hartmann A, Muller M, et al. Downregulation of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity. Int J Clin Exp Pathol. 2014;7(9):6125-32.
53. Paredes J, Albergaria A, Oliveira JT, Jeronimo C, Milanezi F, Schmitt FC. P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation. Clin Cancer Res. 2005;11(16):5869-77. doi: 10.1158/1078-0432.CCR-05-0059.
54. Shimoyama Y, Hirohashi S. Expression of E- and P-cadherin in gastric carcinomas. Cancer Res. 1991;51(8):2185-92.
55. Moreno-Bueno G, Hardisson D, Sarrio D, Sanchez C, Cassia R, Prat J, et al. Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J Pathol. 2003;199(4):471-8. doi: 10.1002/path.1310.
56. Stefansson IM, Salvesen HB, Akslen LA. Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer. J Clin Oncol. 2004;22(7):1242-52. doi: 10.1200/JCO.2004.09.034.
57. Patel IS, Madan P, Getsios S, Bertrand MA, MacCalman CD. Cadherin switching in ovarian cancer progression. Int J Cancer. 2003;106(2):172-7. doi: 10.1002/ijc.11086.
58. Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T, Eguchi H, Ohigashi H, et al. Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res. 2005;65(8):3092-9. doi: 10.1158/0008.5472.CAN-04-3646.
59. Wakita H, Shirahama S, Furukawa F. Distinct P-cadherin expression in cultured normal human keratinocytes and squamous cell carcinoma cell lines. Microsc Res Tech. 1998;43(3):218-23. doi: 10.1002/(SICI)1097-0029(19981101)43:3<218::AID-JEMT3>3.0.CO;2-S.
60. Hardy RG, Tselepis C, Hoyland J, Wallis Y, Pretlow TP, Talbot I, et al. Aberrant P-cadherin expression is an early event in hyperplastic and dysplastic transformation in the colon. Gut. 2002;50(4):513-9.
61. Paredes J, Milanezi F, Viegas L, Amendoeira I, Schmitt F. P-cadherin expression is associated with high-grade ductal carcinoma in situ of the breast. Virchows Arch. 2002;440(1):16-21.
62. Gamallo C, Moreno-Bueno G, Sarrio D, Calero F, Hardisson D, Palacios J. The prognostic significance of P-cadherin in infiltrating ductal breast carcinoma. Mod Pathol. 2001;14(7):650-4.
63. Peralta Soler A, Knudsen KA, Salazar H, Han AC, Keshgegian AA. P-cadherin expression in breast carcinoma indicates poor survival. Cancer. 1999;86(7):1263-72.
64. Turashvili G, McKinney SE, Goktepe O, Leung SC, Huntsman DG, Gelmon KA, et al. P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer. Mod Pathol. 2011;24(1):64-81.
65. Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F. p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch. 2005;447(4):688-94. doi: 10.1007/s00428-005-0010-7.
66. Paredes J, Lopes N, Milanezi F, Schmitt FC. P-cadherin and cytokeratin 5: useful adjunct markers to distinguish basal-like ductal carcinomas in situ. Virchows Arch. 2007;450(1):73-80. doi: 10.1007/s00428-006-0334-y.
67. Arnes JB, Brunet JS, Stefansson I, Begin LR, Wong N, Chappuis PO, et al. Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer. Clin Cancer Res. 2005;11(11):4003-11.
68. Yi S, Yang ZL, Miao X, Zou Q, Li J, Liang L, et al. N-cadherin and P-cadherin are biomarkers for invasion, metastasis, and poor prognosis of gallbladder carcinomas. Pathol Res Pract. 2014;210(6):363-8. doi: 10.1016/j.prp.2014.01.014.
69. Adamczyk A, Niemiec J, Ambicka A, Malecki K, Wysocki WH, Mitus J, et al. Expression of ER/PR/HER2, basal markers and adhesion molecules in primary breast cancer and in lymph nodes metastases: a comparative immunohistochemical analysis. Pol J Pathol. 2012;63(4):228-34.
70. Cheung LW, Yung S, Chan TM, Leung PC, Wong AS. Targeting gonadotropin-releasing hormone receptor inhibits the early step of ovarian cancer metastasis by modulating tumor-mesothelial adhesion. Mol Ther. 2013;21(1):78-90. doi: 10.1038/mt.2012.187.
71. Sun L, Hu H, Peng L, Zhou Z, Zhao X, Pan J, et al. P-cadherin promotes liver metastasis and is associated with poor prognosis in colon cancer. Am J Pathol. 2011;179(1):380-90. doi: 10.1016/j.ajpath.2011.03.046.
72. Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA. A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin Cancer Res. 2007;13(23):7003-11. doi: 10.1158/1078-0432.CCR-07-1263.
73. Davies G, Jiang WG, Mason MD. Cell-cell adhesion molecules and signaling intermediates and their role in the invasive potential of prostate cancer cells. J Urol. 2000;163(3):985-92.
74. Kumper S, Ridley AJ. p120ctn and P-cadherin but not E-cadherin regulate cell motility and invasion of DU145 prostate cancer cells. PLoS One. 2010;5(7):e11801. doi: 10.1371/journal.pone.0011801.
75. Ribeiro AS, Albergaria A, Sousa B, Correia AL, Bracke M, Seruca R, et al. Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells. Oncogene. 2010;29(3):392-402.
76. Paredes J, Stove C, Stove V, Milanezi F, Van Marck V, Derycke L, et al. P-cadherin is up-regulated by the antiestrogen ICI 182,780 and promotes invasion of human breast cancer cells. Cancer Res. 2004;64(22):8309-17. doi: 10.1158/0008-5472.CAN-04-0795.
77. Paredes J, Correia AL, Ribeiro AS, Milanezi F, Cameselle-Teijeiro J, Schmitt FC. Breast carcinomas that co-express E- and P-cadherin are associated with p120-catenin cytoplasmic localisation and poor patient survival. J Clin Pathol. 2008;61(7):856-62. doi: 10.1136/jcp.2007.052704.
78. Sarrio D, Palacios J, Hergueta-Redondo M, Gomez-Lopez G, Cano A, Moreno-Bueno G. Functional characterization of E- and P-cadherin in invasive breast cancer cells. BMC Cancer. 2009;9:74. doi: 10.1186/1471-2407-9-74.
79. Ribeiro AS, Sousa B, Carreto L, Mendes N, Nobre AR, Ricardo S, et al. P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model. J Pathol. 2013;229(5):705-18. doi: 10.1002/path.4143.
80. Cheung LW, Leung PC, Wong AS. Cadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer. Oncogene. 2010;29(16):2427-40. doi: 10.1038/onc.2009.523.
81. Bazellieres E, Conte V, Elosegui-Artola A, Serra-Picamal X, Bintanel-Morcillo M, Roca-Cusachs P, et al. Control of cell-cell forces and collective cell dynamics by the intercellular adhesome. Nat Cell Biol. 2015;17(4):409-20. doi: 10.1038/ncb3135.
82. Cano A, Gamallo C, Kemp CJ, Benito N, Palacios J, Quintanilla M, et al. Expression pattern of the cell adhesion molecules. E-cadherin, P-cadherin and alpha 6 beta 4 intergrin is altered in pre-malignant skin tumors of p53-deficient mice. Int J Cancer. 1996;65(2):254-62. doi: 10.1002/(SICI)1097-0215(19960117)65:2<254::AID-IJC21>3.0.CO;2-C.
83. Pontes-Junior J, Reis ST, Dall'Oglio M, Neves de Oliveira LC, Cury J, Carvalho PA, et al. Evaluation of the expression of integrins and cell adhesion molecules through tissue microarray in lymph node metastases of prostate cancer. J Carcinog. 2009;8:3.
84. Bagutti C, Speight PM, Watt FM. Comparison of integrin, cadherin, and catenin expression in squamous cell carcinomas of the oral cavity. J Pathol. 1998;186(1):8-16. doi: 10.1002/(SICI)1096-9896(199809)186:1<8::AID-PATH156>3.0.CO;2-H.
85. Ip CK, Yung S, Chan TM, Tsao SW, Wong AS. p70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/b1 integrin signaling activation. Oncotarget. 2014;5(19):9133-49.
86. Cheung LW, Mak AS, Cheung AN, Ngan HY, Leung PC, Wong AS. P-cadherin cooperates with insulin-like growth factor-1 receptor to promote metastatic signaling of gonadotropin-releasing hormone in ovarian cancer via p120 catenin. Oncogene. 2011;30(26):2964-74. doi: 10.1038/onc.2011.7.
87. Switzer CH, Cheng RY, Ridnour LA, Glynn SA, Ambs S, Wink DA. Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Res. 2012;14(5):R125. doi: 10.1186/bcr3319.
88. Switzer CH, Glynn SA, Cheng RY, Ridnour LA, Green JE, Ambs S, et al. S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer. Mol Cancer Res. 2012;10(9):1203-15. doi: 10.1158/1541-7786.MCR-12-0124.
89. Fagotto F. Looking beyond the Wnt pathway for the deep nature of beta-catenin. EMBO Rep. 2013;14(5):422-33. doi: 10.1038/embor.2013.45.
90. Lysne D, Johns J, Walker A, Ecker R, Fowler C, Lawson KR. P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes. Oncol Rep. 2014;32(6):2541-8. doi: 10.3892/or.2014.3545.
91. Thuault S, Hayashi S, Lagirand-Cantaloube J, Plutoni C, Comunale F, Delattre O, et al. P-cadherin is a direct PAX3-FOXO1A target involved in alveolar rhabdomyosarcoma aggressiveness. Oncogene. 2013;32(15):1876-87. doi: 10.1038/onc.2012.217.
92. Fenouille N, Tichet M, Dufies M, Pottier A, Mogha A, Soo JK, et al. The epithelial-mesenchymal transition (EMT) regulatory factor SLUG (SNAI2) is a downstream target of SPARC and AKT in promoting melanoma cell invasion. PLoS One. 2012;7(7):e40378. doi: 10.1371/journal.pone.0040378.
93. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-11. doi: 10.1038/35102167.
94. Sousa B, Ribeiro AS, Nobre AR, Lopes N, Martins D, Pinheiro C, et al. The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype. BMC Cancer. 2014;14:734-746.
95. Albergaria A, Ribeiro AS, Pinho S, Milanezi F, Carneiro V, Sousa B, et al. ICI 182,780 induces P-cadherin overexpression in breast cancer cells through chromatin remodelling at the promoter level: a role for C/EBPbeta in CDH3 gene activation. Hum Mol Genet. 2010;19(13):2554-66. doi: 10.1093/hmg/ddq134.
96. Faraldo MM, Teuliere J, Deugnier MA, Birchmeier W, Huelsken J, Thiery JP, et al. beta-Catenin regulates P-cadherin expression in mammary basal epithelial cells. FEBS Lett. 2007;581(5):831-6.
97. Shimomura Y, Wajid M, Shapiro L, Christiano AM. P-cadherin is a p63 target gene with a crucial role in the developing human limb bud and hair follicle. Development. 2008;135(4):743-53.
98. Proia TA, Keller PJ, Gupta PB, Klebba I, Jones AD, Sedic M, et al. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell. 2011;8(2):149-63.
99. Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, et al. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A. 2008;105(5):1680-5. doi: 10.1073/pnas.0711613105.
100. Gorski JJ, James CR, Quinn JE, Stewart GE, Staunton KC, Buckley NE, et al. BRCA1 transcriptionally regulates genes associated with the basal-like phenotype in breast cancer. Breast Cancer Res Treat. 2009;122(3):721-31.
101. Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009;15(8):907-13.
102. Molyneux G, Geyer FC, Magnay FA, McCarthy A, Kendrick H, Natrajan R, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell. 2010;7(3):403-17. doi: 10.1016/j.stem.2010.07.010.
103. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004;432(7015):324-31. doi: 10.1038/nature03100.
104. Yoshioka H, Yamamoto S, Hanaoka H, Iida Y, Paudyal P, Higuchi T, et al. In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy. Cancer Immunol Immunother. 2012;61(8):1211-20. doi: 10.1007/s00262-011-1186-0.
105. Park J, Park E, Han SW, Im SA, Kim TY, Kim WH, et al. Down-regulation of P-cadherin with PF-03732010 inhibits cell migration and tumor growth in gastric cancer. Invest New Drugs. 2011;30(4):1404-12.
106. Zhang CC, Yan Z, Zhang Q, Kuszpit K, Zasadny K, Qiu M, et al. PF-03732010: a fully human monoclonal antibody against P-cadherin with antitumor and antimetastatic activity. Clin Cancer Res. 2010;16(21):5177-88. doi: 10.1158/1078-0432.CCR-10-1343.
107. http://clinicaltrials.gov/ct2/show/results/NCT00557505. Accessed 22 April 2015.
108. Bernardes N, Ribeiro AS, Abreu S, Mota B, Matos RG, Arraiano CM, et al. The bacterial protein azurin impairs invasion and FAK/Src signaling in P-cadherin-overexpressing breast cancer cell models. PLoS One. 2013;8(7):e69023. doi: 10.1371/journal.pone.0069023.
109. Bernardes N, Ribeiro AS, Abreu S, Vieira AF, Carreto L, Santos M, et al. High-throughput molecular profiling of a P-cadherin overexpressing breast cancer model reveals new targets for the anti-cancer bacterial protein azurin. Int J Biochem Cell Biol. 2014;50:1-9. doi: 10.1016/j.biocel.2014.01.023.
110. Warso MA, Richards JM, Mehta D, Christov K, Schaeffer C, Rae Bressler L, et al. A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours. Br J Cancer. 2013;108(5):1061-70. doi: 10.1038/bjc.2013.74.
111. Obama K, Ura K, Li M, Katagiri T, Tsunoda T, Nomura A, et al. Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma. Hepathology. 2005;41(6):133-48.