Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene

Douglas B. Stairs; Lauren J. Bayne; Ben Rhoades; Maria E. Vega; Todd J. Waldron; Jiri Kalabis; Andres Klein-Szanto; Ju Seog Lee; Jonathan P. Katz; J. Alan Diehl; Albert B. Reynolds; Robert H. Vonderheide; Anil K. Rustgi

doi:10.1016/j.ccr.2011.02.007

Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene

Douglas B. Stairs
, Lauren J. Bayne
, Ben Rhoades
, Maria E. Vega
, Todd J. Waldron
, Jiri Kalabis
, Andres Klein-Szanto
, Ju Seog Lee
, Jonathan P. Katz
, J. Alan Diehl
, Albert B. Reynolds
, Robert H. Vonderheide
, Anil K. Rustgi

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

Abstract

p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNFα). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.

Original language	English (US)
Pages (from-to)	470-483
Number of pages	14
Journal	Cancer Cell
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2011.02.007
State	Published - Apr 12 2011

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

Access to Document

10.1016/j.ccr.2011.02.007

Cite this

Stairs, D. B., Bayne, L. J., Rhoades, B., Vega, M. E., Waldron, T. J., Kalabis, J., Klein-Szanto, A., Lee, J. S., Katz, J. P., Diehl, J. A., Reynolds, A. B., Vonderheide, R. H., & Rustgi, A. K. (2011). Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene. Cancer Cell, 19(4), 470-483. https://doi.org/10.1016/j.ccr.2011.02.007

@article{5d2db70494714207bf93de29ce06a144,

title = "Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene",

abstract = "p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNFα). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.",

author = "Stairs, \{Douglas B.\} and Bayne, \{Lauren J.\} and Ben Rhoades and Vega, \{Maria E.\} and Waldron, \{Todd J.\} and Jiri Kalabis and Andres Klein-Szanto and Lee, \{Ju Seog\} and Katz, \{Jonathan P.\} and Diehl, \{J. Alan\} and Reynolds, \{Albert B.\} and Vonderheide, \{Robert H.\} and Rustgi, \{Anil K.\}",

note = "Funding Information: This work was supported by the following NIH grants: NCI P01-CA098101 Mechanisms in Esophageal Carcinogenesis (to D.B.S., J.K., M.E.V., J.P.K., A.K.-S., J.A.D., and A.K.R.); NCI F32-CA1308513 and NCI K99/R00-CA138498 (to D.B.S.); NCI T32-CA115299 (to J.K.); NCI U01-CA143056 (to A.K.R.); NCI P30 Abramson Cancer Center pilot grant NCI P30-CA016520 (to R.H.V.); NIDDK R01-DK069984 (to J.P.K.); and the NIDDK P30-DK050306 Center for Molecular Studies in Digestive and Liver Diseases and the American Cancer Society Research Professorship (to A.K.R.). Work contributed by the Reynolds lab was supported by NCI CA111947, CA055724, and the Vanderbilt GI SPORE (50CA95103). We wish to thank the Morphology (S. Mitchell), Molecular Biology/Gene Expression, Transgenic/Chimeric Mouse, Microarray and Cell Culture Core Facilities as well as Amy Ziober in the Department of Pathology and Laboratory Medicine. We are also grateful to members of the Rustgi lab for helpful discussions. ",

year = "2011",

month = apr,

day = "12",

doi = "10.1016/j.ccr.2011.02.007",

language = "English (US)",

volume = "19",

pages = "470--483",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

}

Stairs, DB, Bayne, LJ, Rhoades, B, Vega, ME, Waldron, TJ, Kalabis, J, Klein-Szanto, A, Lee, JS, Katz, JP, Diehl, JA, Reynolds, AB, Vonderheide, RH & Rustgi, AK 2011, 'Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene', Cancer Cell, vol. 19, no. 4, pp. 470-483. https://doi.org/10.1016/j.ccr.2011.02.007

TY - JOUR

T1 - Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene

AU - Stairs, Douglas B.

AU - Bayne, Lauren J.

AU - Rhoades, Ben

AU - Vega, Maria E.

AU - Waldron, Todd J.

AU - Kalabis, Jiri

AU - Klein-Szanto, Andres

AU - Lee, Ju Seog

AU - Katz, Jonathan P.

AU - Diehl, J. Alan

AU - Reynolds, Albert B.

AU - Vonderheide, Robert H.

AU - Rustgi, Anil K.

N1 - Funding Information: This work was supported by the following NIH grants: NCI P01-CA098101 Mechanisms in Esophageal Carcinogenesis (to D.B.S., J.K., M.E.V., J.P.K., A.K.-S., J.A.D., and A.K.R.); NCI F32-CA1308513 and NCI K99/R00-CA138498 (to D.B.S.); NCI T32-CA115299 (to J.K.); NCI U01-CA143056 (to A.K.R.); NCI P30 Abramson Cancer Center pilot grant NCI P30-CA016520 (to R.H.V.); NIDDK R01-DK069984 (to J.P.K.); and the NIDDK P30-DK050306 Center for Molecular Studies in Digestive and Liver Diseases and the American Cancer Society Research Professorship (to A.K.R.). Work contributed by the Reynolds lab was supported by NCI CA111947, CA055724, and the Vanderbilt GI SPORE (50CA95103). We wish to thank the Morphology (S. Mitchell), Molecular Biology/Gene Expression, Transgenic/Chimeric Mouse, Microarray and Cell Culture Core Facilities as well as Amy Ziober in the Department of Pathology and Laboratory Medicine. We are also grateful to members of the Rustgi lab for helpful discussions.

PY - 2011/4/12

Y1 - 2011/4/12

N2 - p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNFα). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.

AB - p120-catenin (p120ctn) interacts with E-cadherin, but to our knowledge, no formal proof that p120ctn functions as a bona fide tumor suppressor gene has emerged to date. We report herein that p120ctn loss leads to tumor development in mice. We have generated a conditional knockout model of p120ctn whereby mice develop preneoplastic and neoplastic lesions in the oral cavity, esophagus, and squamous forestomach. Tumor-derived cells secrete granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNFα). The tumors contain significant desmoplasia and immune cell infiltration. Immature myeloid cells comprise a significant percentage of the immune cells present and likely participate in fostering a favorable tumor microenvironment, including the activation of fibroblasts.

UR - https://www.scopus.com/pages/publications/79953736599

UR - https://www.scopus.com/pages/publications/79953736599#tab=citedBy

U2 - 10.1016/j.ccr.2011.02.007

DO - 10.1016/j.ccr.2011.02.007

M3 - Article

C2 - 21481789

AN - SCOPUS:79953736599

SN - 1535-6108

VL - 19

SP - 470

EP - 483

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor Gene

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this