Modulation of the tumor suppressor protein α-catenin by ischemic microenvironment

Claire L. Plumb, Una Adamcic, Siranoush Shahrzad, Kanwal Minhas, Sirin A I Adham, Brenda L. Coomber

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Dysregulation or mislocalization of cell adhesion molecules and their regulators, such as E-cadherin, β-catenin, and α-catenin, usually correlates with loss of polarity, dedifferentiation, invasive tumor growth, and metastasis. A subpopulation of α-catenin-negative cells within the DLD-1 colorectal carcinoma cell line causes it to display a heterogeneous morphological makeup, thus providing an excellent model system in which to investigate the role of α-catenin in tumorigenesis. We re-established expression of α-catenin protein in an α-catenin-deficient subpopulation of the DLD-1 cell line and used it to demonstrate that loss of α-catenin resulted in increased in vitro tumorigenic characteristics (increased soft agarose colony formation, clonogenic survival after suspension, and survival in suspension). When the cells were used to form tumor xenografts, those lacking α-catenin showed faster growth rates because of increased cellular cycling but not increased tumor microvascular recruitment. α-Catenin-expressing cells were preferentially located in well perfused areas of xenografts when tumors were formed from mixed α-cateninpositive and -negative cells. We therefore evaluated the role of the ischemic tumor microenvironment on α-catenin expression and demonstrated that cells lose expression of α-catenin after prolonged exposure in vitro to hypoglycemic conditions. Our findings illustrate that the tumor microenvironment is a potent modulator of tumor suppressor expression, which has implications for localized nutrient deficiency and ischemia-induced cancer progression.

Original languageEnglish
Pages (from-to)1662-1674
Number of pages13
JournalAmerican Journal of Pathology
Volume175
Issue number4
DOIs
Publication statusPublished - 2009

Fingerprint

Tumor Suppressor Proteins
Catenins
Neoplasms
Tumor Microenvironment
Heterografts
Suspensions
Cell Line
Cell Adhesion Molecules
Cadherins
Growth
Hypoglycemic Agents
Sepharose
Colorectal Neoplasms
Carcinogenesis
Ischemia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Modulation of the tumor suppressor protein α-catenin by ischemic microenvironment. / Plumb, Claire L.; Adamcic, Una; Shahrzad, Siranoush; Minhas, Kanwal; Adham, Sirin A I; Coomber, Brenda L.

In: American Journal of Pathology, Vol. 175, No. 4, 2009, p. 1662-1674.

Research output: Contribution to journalArticle

Plumb, Claire L. ; Adamcic, Una ; Shahrzad, Siranoush ; Minhas, Kanwal ; Adham, Sirin A I ; Coomber, Brenda L. / Modulation of the tumor suppressor protein α-catenin by ischemic microenvironment. In: American Journal of Pathology. 2009 ; Vol. 175, No. 4. pp. 1662-1674.
@article{a1c0fe23ed61497287834954c7d8ba07,
title = "Modulation of the tumor suppressor protein α-catenin by ischemic microenvironment",
abstract = "Dysregulation or mislocalization of cell adhesion molecules and their regulators, such as E-cadherin, β-catenin, and α-catenin, usually correlates with loss of polarity, dedifferentiation, invasive tumor growth, and metastasis. A subpopulation of α-catenin-negative cells within the DLD-1 colorectal carcinoma cell line causes it to display a heterogeneous morphological makeup, thus providing an excellent model system in which to investigate the role of α-catenin in tumorigenesis. We re-established expression of α-catenin protein in an α-catenin-deficient subpopulation of the DLD-1 cell line and used it to demonstrate that loss of α-catenin resulted in increased in vitro tumorigenic characteristics (increased soft agarose colony formation, clonogenic survival after suspension, and survival in suspension). When the cells were used to form tumor xenografts, those lacking α-catenin showed faster growth rates because of increased cellular cycling but not increased tumor microvascular recruitment. α-Catenin-expressing cells were preferentially located in well perfused areas of xenografts when tumors were formed from mixed α-cateninpositive and -negative cells. We therefore evaluated the role of the ischemic tumor microenvironment on α-catenin expression and demonstrated that cells lose expression of α-catenin after prolonged exposure in vitro to hypoglycemic conditions. Our findings illustrate that the tumor microenvironment is a potent modulator of tumor suppressor expression, which has implications for localized nutrient deficiency and ischemia-induced cancer progression.",
author = "Plumb, {Claire L.} and Una Adamcic and Siranoush Shahrzad and Kanwal Minhas and Adham, {Sirin A I} and Coomber, {Brenda L.}",
year = "2009",
doi = "10.2353/ajpath.2009.090007",
language = "English",
volume = "175",
pages = "1662--1674",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Modulation of the tumor suppressor protein α-catenin by ischemic microenvironment

AU - Plumb, Claire L.

AU - Adamcic, Una

AU - Shahrzad, Siranoush

AU - Minhas, Kanwal

AU - Adham, Sirin A I

AU - Coomber, Brenda L.

PY - 2009

Y1 - 2009

N2 - Dysregulation or mislocalization of cell adhesion molecules and their regulators, such as E-cadherin, β-catenin, and α-catenin, usually correlates with loss of polarity, dedifferentiation, invasive tumor growth, and metastasis. A subpopulation of α-catenin-negative cells within the DLD-1 colorectal carcinoma cell line causes it to display a heterogeneous morphological makeup, thus providing an excellent model system in which to investigate the role of α-catenin in tumorigenesis. We re-established expression of α-catenin protein in an α-catenin-deficient subpopulation of the DLD-1 cell line and used it to demonstrate that loss of α-catenin resulted in increased in vitro tumorigenic characteristics (increased soft agarose colony formation, clonogenic survival after suspension, and survival in suspension). When the cells were used to form tumor xenografts, those lacking α-catenin showed faster growth rates because of increased cellular cycling but not increased tumor microvascular recruitment. α-Catenin-expressing cells were preferentially located in well perfused areas of xenografts when tumors were formed from mixed α-cateninpositive and -negative cells. We therefore evaluated the role of the ischemic tumor microenvironment on α-catenin expression and demonstrated that cells lose expression of α-catenin after prolonged exposure in vitro to hypoglycemic conditions. Our findings illustrate that the tumor microenvironment is a potent modulator of tumor suppressor expression, which has implications for localized nutrient deficiency and ischemia-induced cancer progression.

AB - Dysregulation or mislocalization of cell adhesion molecules and their regulators, such as E-cadherin, β-catenin, and α-catenin, usually correlates with loss of polarity, dedifferentiation, invasive tumor growth, and metastasis. A subpopulation of α-catenin-negative cells within the DLD-1 colorectal carcinoma cell line causes it to display a heterogeneous morphological makeup, thus providing an excellent model system in which to investigate the role of α-catenin in tumorigenesis. We re-established expression of α-catenin protein in an α-catenin-deficient subpopulation of the DLD-1 cell line and used it to demonstrate that loss of α-catenin resulted in increased in vitro tumorigenic characteristics (increased soft agarose colony formation, clonogenic survival after suspension, and survival in suspension). When the cells were used to form tumor xenografts, those lacking α-catenin showed faster growth rates because of increased cellular cycling but not increased tumor microvascular recruitment. α-Catenin-expressing cells were preferentially located in well perfused areas of xenografts when tumors were formed from mixed α-cateninpositive and -negative cells. We therefore evaluated the role of the ischemic tumor microenvironment on α-catenin expression and demonstrated that cells lose expression of α-catenin after prolonged exposure in vitro to hypoglycemic conditions. Our findings illustrate that the tumor microenvironment is a potent modulator of tumor suppressor expression, which has implications for localized nutrient deficiency and ischemia-induced cancer progression.

UR - http://www.scopus.com/inward/record.url?scp=73549115416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73549115416&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2009.090007

DO - 10.2353/ajpath.2009.090007

M3 - Article

VL - 175

SP - 1662

EP - 1674

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -