Pro-tumorigenic phosphorylation of p120 catenin in renal and breast cancer

Antonis Kourtidis, Masahiro Yanagisawa, Deborah Huveldt, John A III Copland, Panagiotis Z Anastasiadis

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated.

Original languageEnglish (US)
Article numbere0129964
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 11 2015

Fingerprint

kidney neoplasms
Phosphorylation
Kidney Neoplasms
breast neoplasms
phosphorylation
Breast Neoplasms
Tumors
neoplasms
cadherins
Cadherins
Neoplasms
Tissue
tyrosine
Tyrosine
antibodies
oncogenes
protein phosphorylation
Antibodies
cell adhesion
threonine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pro-tumorigenic phosphorylation of p120 catenin in renal and breast cancer. / Kourtidis, Antonis; Yanagisawa, Masahiro; Huveldt, Deborah; Copland, John A III; Anastasiadis, Panagiotis Z.

In: PLoS One, Vol. 10, No. 6, e0129964, 11.06.2015.

Research output: Contribution to journalArticle

Kourtidis, Antonis ; Yanagisawa, Masahiro ; Huveldt, Deborah ; Copland, John A III ; Anastasiadis, Panagiotis Z. / Pro-tumorigenic phosphorylation of p120 catenin in renal and breast cancer. In: PLoS One. 2015 ; Vol. 10, No. 6.
@article{effbb65b224943c881564de071a6d27a,
title = "Pro-tumorigenic phosphorylation of p120 catenin in renal and breast cancer",
abstract = "Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated.",
author = "Antonis Kourtidis and Masahiro Yanagisawa and Deborah Huveldt and Copland, {John A III} and Anastasiadis, {Panagiotis Z}",
year = "2015",
month = "6",
day = "11",
doi = "10.1371/journal.pone.0129964",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Pro-tumorigenic phosphorylation of p120 catenin in renal and breast cancer

AU - Kourtidis, Antonis

AU - Yanagisawa, Masahiro

AU - Huveldt, Deborah

AU - Copland, John A III

AU - Anastasiadis, Panagiotis Z

PY - 2015/6/11

Y1 - 2015/6/11

N2 - Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated.

AB - Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated.

UR - http://www.scopus.com/inward/record.url?scp=84936123957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936123957&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0129964

DO - 10.1371/journal.pone.0129964

M3 - Article

C2 - 26067913

AN - SCOPUS:84936123957

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e0129964

ER -