Home LiteratureArticle Details
PMID: 15161659 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer.

The American journal of pathology ·Vol. 164 ·No. 6 ·2004-06-00 ·Pages 2269-78

Shibata T, Kokubu A, Sekine S, Kanai Y, Hirohashi S

Abstract

In a search for signaling molecules that act downstream of E-cadherin inactivation in cancer, we examined the expression and localization of E-cadherin-associated proteins in lobular carcinoma, in which the E-cadherin gene is frequently inactivated, and found that E-cadherin down-regulation correlated with the cytoplasmic localization of p120ctn. Similar cytoplasmic localization of p120ctn and growth factor-induced accumulation of tyrosine-phosphorylated p120ctn in the protrusive domain were observed in E-cadherin-deficient breast cancer cells. Down-regulation of endogenous p120ctn by RNA interference promoted stress fiber formation and induced a flattened morphology with an increase of Rho-GTPase activity; it also reduced the development of membranous protrusions and migratory activity in E-cadherin-deficient breast cancer cells. Inactivation of E-cadherin in cancer cells is associated with the conversion from epithelial to mesenchymal phenotype, which also occurs in physiological conditions such as developmental processes. Cytoplasmic localization of p120ctn accompanied by E-cadherin down-regulation was observed in mesoderm cells that had undergone epithelial-mesenchymal transition during early mouse embryogenesis. Collectively, our results suggest that cytoplasmic p120ctn may contribute to the invasive phenotype of E-cadherin-deficient breast cancer cells.

MeSH Terms
Base Sequence Breast Neoplasms/genetics,pathology Cadherins/genetics,physiology Carcinoma, Lobular/genetics,pathology Catenins Cell Adhesion Molecules/analysis,genetics Cell Division Cell Movement Female Humans Immunohistochemistry Neoplasm Invasiveness/genetics,pathology Oligodeoxyribonucleotides Phosphoproteins/analysis,genetics Phosphorylation Phosphotyrosine/metabolism Plasmids RNA, Small Interfering/genetics Transfection
Chemicals
Cadherins Catenins Cell Adhesion Molecules Oligodeoxyribonucleotides Phosphoproteins RNA, Small Interfering delta catenin Phosphotyrosine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shibata Tatsuhiro
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kokubu Akiko
Sekine Shigeki
Kanai Yae
Hirohashi Setsuo
References (49)
49 references, click to expand
  1. Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells.
    J Cell Biol. 2003 Nov 10;163(3):535-45 PMID: 14610056
  2. Pathogenesis of Paget's disease: epidermal heregulin-alpha, motility factor, and the HER receptor family.
    J Natl Cancer Inst. 2000 Apr 19;92(8):622-8 PMID: 10772679
  3. Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis.
    Development. 1989 Feb;105(2):271-7 PMID: 2806126
  4. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.
    J Cell Biol. 1991 Apr;113(1):173-85 PMID: 2007622
  5. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.
    Cell. 1991 Jul 12;66(1):107-19 PMID: 2070412
  6. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo.
    Oncogene. 1992 Dec;7(12):2439-45 PMID: 1334250
  7. E-cadherin gene mutations in human gastric carcinoma cell lines.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1858-62 PMID: 8127895
  8. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas.
    Cancer Res. 1994 Jul 15;54(14):3845-52 PMID: 8033105
  9. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.
    J Cell Biol. 1994 Oct;127(1):247-56 PMID: 7929567
  10. Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast.
    Jpn J Cancer Res. 1994 Oct;85(10):1035-9 PMID: 7961105
  11. Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes.
    Mol Cell Biol. 1994 Dec;14(12):8333-42 PMID: 7526156
  12. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes.
    J Cell Biol. 1995 Mar;128(5):949-57 PMID: 7876318
  13. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death.
    J Cell Biol. 1995 Apr;129(2):489-506 PMID: 7721948
  14. Morphogenetic roles of classic cadherins.
    Curr Opin Cell Biol. 1995 Oct;7(5):619-27 PMID: 8573335
  15. p120 catenin regulates the actin cytoskeleton via Rho family GTPases.
    J Cell Biol. 2000 Aug 7;150(3):567-80 PMID: 10931868
  16. Inhibition of RhoA by p120 catenin.
    Nat Cell Biol. 2000 Sep;2(9):637-44 PMID: 10980705
  17. Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling.
    Cancer Res. 2001 Jan 1;61(1):278-84 PMID: 11196175
  18. p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion.
    J Cell Sci. 2001 Feb;114(Pt 4):695-707 PMID: 11171375
  19. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.
    Mol Cell. 2001 Jun;7(6):1267-78 PMID: 11430829
  20. RhoA is required for monocyte tail retraction during transendothelial migration.
    J Cell Biol. 2001 Jul 9;154(1):147-60 PMID: 11448997
  21. Identification of Src phosphorylation sites in the catenin p120ctn.
    J Biol Chem. 2001 Jul 27;276(30):28006-13 PMID: 11382764
  22. The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition.
    Mol Cell Biol. 2001 Dec;21(23):8184-8 PMID: 11689706
  23. Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila.
    Development. 2002 Aug;129(16):3771-82 PMID: 12135916
  24. A novel role for p120 catenin in E-cadherin function.
    J Cell Biol. 2002 Nov 11;159(3):465-76 PMID: 12427869
  25. An alternatively spliced cadherin-11 enhances human breast cancer cell invasion.
    Cancer Res. 2002 Nov 15;62(22):6688-97 PMID: 12438268
  26. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations.
    Am J Pathol. 2002 Dec;161(6):1997-2001 PMID: 12466115
  27. Rho GTPases in cell biology.
    Nature. 2002 Dec 12;420(6916):629-35 PMID: 12478284
  28. Altered expression of the catenin p120 in human cancer: implications for tumor progression.
    Differentiation. 2002 Dec;70(9-10):583-9 PMID: 12492499
  29. p120 Catenin is required for growth factor-dependent cell motility and scattering in epithelial cells.
    Mol Biol Cell. 2003 May;14(5):1964-77 PMID: 12802068
  30. A core function for p120-catenin in cadherin turnover.
    J Cell Biol. 2003 Nov 10;163(3):525-34 PMID: 14610055
  31. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers.
    EMBO J. 1995 Dec 15;14(24):6107-15 PMID: 8557030
  32. Cell adhesion: the molecular basis of tissue architecture and morphogenesis.
    Cell. 1996 Feb 9;84(3):345-57 PMID: 8608588
  33. Cadherin-mediated cell adhesion and cell motility in Drosophila trachea regulated by the transcription factor Escargot.
    Development. 1996 Dec;122(12):3697-705 PMID: 9012491
  34. Interaction of the adaptor protein Shc and the adhesion molecule cadherin.
    J Biol Chem. 1997 May 23;272(21):13463-6 PMID: 9153187
  35. Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho-induced cytoskeletal reorganization.
    J Cell Biol. 1997 Aug 25;138(4):913-26 PMID: 9265656
  36. The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin.
    Am J Pathol. 1998 Jan;152(1):75-82 PMID: 9422525
  37. The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn.
    J Cell Biol. 1998 May 4;141(3):779-89 PMID: 9566976
  38. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers.
    Am J Pathol. 1998 Aug;153(2):333-9 PMID: 9708792
  39. Dynamic behavior of the cadherin-based cell-cell adhesion system during Drosophila gastrulation.
    Dev Biol. 1998 Nov 15;203(2):435-50 PMID: 9808792
  40. Misexpression of the catenin p120(ctn)1A perturbs Xenopus gastrulation but does not elicit Wnt-directed axis specification.
    Dev Biol. 1999 Mar 15;207(2):350-63 PMID: 10068468
  41. Rho GTPases control polarity, protrusion, and adhesion during cell movement.
    J Cell Biol. 1999 Mar 22;144(6):1235-44 PMID: 10087266
  42. p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells.
    J Cell Biol. 1999 May 3;145(3):551-62 PMID: 10225956
  43. Nuclear localization of the p120(ctn) Armadillo-like catenin is counteracted by a nuclear export signal and by E-cadherin expression.
    Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7980-5 PMID: 10393933
  44. Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility.
    Oncogene. 1999 Jul 29;18(30):4301-12 PMID: 10439038
  45. Up-regulated cytoplasmic expression, with reduced membranous distribution, of the src substrate p120(ctn) in gastric carcinoma.
    J Pathol. 1999 Oct;189(2):180-5 PMID: 10547572
  46. Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion.
    J Cell Biol. 2000 Jan 10;148(1):189-202 PMID: 10629228
  47. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression.
    Nat Cell Biol. 2000 Feb;2(2):76-83 PMID: 10655586
  48. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells.
    Nat Cell Biol. 2000 Feb;2(2):84-9 PMID: 10655587
  49. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species.
    EMBO J. 1989 Jun;8(6):1711-7 PMID: 2788574
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63783-2
Published
2004-06-00
Pages
2269-78
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1615772
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63783-2 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2