Research ExplorerPublicationsTransforming growth factor-beta receptor inhibition enhances...

Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition

Standard

Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition. / Lacher, Markus D; Tiirikainen, Maarit I; Saunier, Elise F; Christian, Christine; Anders, Mario; Oft, Martin; Balmain, Allan; Akhurst, Rosemary J; Korn, Wolfgang Michael.

In: CANCER RES, Vol. 66, No. 3, 01.02.2006, p. 1648-57.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lacher, MD, Tiirikainen, MI, Saunier, EF, Christian, C, Anders, M, Oft, M, Balmain, A, Akhurst, RJ & Korn, WM 2006, 'Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition', CANCER RES, vol. 66, no. 3, pp. 1648-57. https://doi.org/10.1158/0008-5472.CAN-05-2328

APA

Lacher, M. D., Tiirikainen, M. I., Saunier, E. F., Christian, C., Anders, M., Oft, M., Balmain, A., Akhurst, R. J., & Korn, W. M. (2006). Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition. CANCER RES, 66(3), 1648-57. https://doi.org/10.1158/0008-5472.CAN-05-2328

Vancouver

Lacher MD, Tiirikainen MI, Saunier EF, Christian C, Anders M, Oft M et al. Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition. CANCER RES. 2006 Feb 1;66(3):1648-57. https://doi.org/10.1158/0008-5472.CAN-05-2328

Bibtex

@article{ffbc6eea4a474170aff9e94cf833df74,
title = "Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition",
abstract = "Expression of the Coxsackie and Adenovirus Receptor (CAR) is frequently reduced in carcinomas, resulting in decreased susceptibility of such tumors to infection with therapeutic adenoviruses. Because CAR participates physiologically in the formation of tight-junction protein complexes, we examined whether molecular mechanisms known to down-regulate cell-cell adhesions cause loss of CAR expression. Transforming growth factor-beta (TGF-beta)-mediated epithelial-mesenchymal transition (EMT) is a phenomenon associated with tumor progression that is characterized by loss of epithelial-type cell-cell adhesion molecules (including E-cadherin and the tight junction protein ZO-1), gain of mesenchymal biochemical markers, such as fibronectin, and acquisition of a spindle cell phenotype. CAR expression is reduced in tumor cells that have undergone EMT in response to TGF-beta. This down-regulation results from repression of CAR gene transcription, whereas altered RNA stability and increased proteasomal protein degradation play no role. Loss of CAR expression in response to TGF-beta is accompanied by reduced susceptibility to adenovirus infection. Indeed, treatment of carcinoma cells with LY2109761, a specific pharmacologic inhibitor of TGF-beta receptor types I and II kinases, resulted in increased CAR RNA and protein levels as well as improved infectability with adenovirus. This was observed in cells induced to undergo EMT by addition of exogenous TGF-beta and in those that were transformed by endogenous autocrine/paracrine TGF-beta. These findings show down-regulation of CAR in the context of EMT and suggest that combination of therapeutic adenoviruses and TGF-beta receptor inhibitors could be an efficient anticancer strategy.",
keywords = "Adenoviridae, Animals, Carcinoma, Coxsackie and Adenovirus Receptor-Like Membrane Protein, Cricetinae, Epithelial Cells, Female, Humans, Mammary Neoplasms, Experimental, Mesoderm, Mice, Phosphatidylinositol 3-Kinases, Receptors, Transforming Growth Factor beta, Receptors, Virus, Skin Neoplasms, Transcription, Genetic, Transforming Growth Factor beta, Up-Regulation",
author = "Lacher, {Markus D} and Tiirikainen, {Maarit I} and Saunier, {Elise F} and Christine Christian and Mario Anders and Martin Oft and Allan Balmain and Akhurst, {Rosemary J} and Korn, {Wolfgang Michael}",
year = "2006",
month = feb,
day = "1",
doi = "10.1158/0008-5472.CAN-05-2328",
language = "English",
volume = "66",
pages = "1648--57",
journal = "CANCER RES",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Transforming growth factor-beta receptor inhibition enhances adenoviral infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus Receptor in conjunction with reversal of epithelial-mesenchymal transition

AU - Lacher, Markus D

AU - Tiirikainen, Maarit I

AU - Saunier, Elise F

AU - Christian, Christine

AU - Anders, Mario

AU - Oft, Martin

AU - Balmain, Allan

AU - Akhurst, Rosemary J

AU - Korn, Wolfgang Michael

PY - 2006/2/1

Y1 - 2006/2/1

N2 - Expression of the Coxsackie and Adenovirus Receptor (CAR) is frequently reduced in carcinomas, resulting in decreased susceptibility of such tumors to infection with therapeutic adenoviruses. Because CAR participates physiologically in the formation of tight-junction protein complexes, we examined whether molecular mechanisms known to down-regulate cell-cell adhesions cause loss of CAR expression. Transforming growth factor-beta (TGF-beta)-mediated epithelial-mesenchymal transition (EMT) is a phenomenon associated with tumor progression that is characterized by loss of epithelial-type cell-cell adhesion molecules (including E-cadherin and the tight junction protein ZO-1), gain of mesenchymal biochemical markers, such as fibronectin, and acquisition of a spindle cell phenotype. CAR expression is reduced in tumor cells that have undergone EMT in response to TGF-beta. This down-regulation results from repression of CAR gene transcription, whereas altered RNA stability and increased proteasomal protein degradation play no role. Loss of CAR expression in response to TGF-beta is accompanied by reduced susceptibility to adenovirus infection. Indeed, treatment of carcinoma cells with LY2109761, a specific pharmacologic inhibitor of TGF-beta receptor types I and II kinases, resulted in increased CAR RNA and protein levels as well as improved infectability with adenovirus. This was observed in cells induced to undergo EMT by addition of exogenous TGF-beta and in those that were transformed by endogenous autocrine/paracrine TGF-beta. These findings show down-regulation of CAR in the context of EMT and suggest that combination of therapeutic adenoviruses and TGF-beta receptor inhibitors could be an efficient anticancer strategy.

AB - Expression of the Coxsackie and Adenovirus Receptor (CAR) is frequently reduced in carcinomas, resulting in decreased susceptibility of such tumors to infection with therapeutic adenoviruses. Because CAR participates physiologically in the formation of tight-junction protein complexes, we examined whether molecular mechanisms known to down-regulate cell-cell adhesions cause loss of CAR expression. Transforming growth factor-beta (TGF-beta)-mediated epithelial-mesenchymal transition (EMT) is a phenomenon associated with tumor progression that is characterized by loss of epithelial-type cell-cell adhesion molecules (including E-cadherin and the tight junction protein ZO-1), gain of mesenchymal biochemical markers, such as fibronectin, and acquisition of a spindle cell phenotype. CAR expression is reduced in tumor cells that have undergone EMT in response to TGF-beta. This down-regulation results from repression of CAR gene transcription, whereas altered RNA stability and increased proteasomal protein degradation play no role. Loss of CAR expression in response to TGF-beta is accompanied by reduced susceptibility to adenovirus infection. Indeed, treatment of carcinoma cells with LY2109761, a specific pharmacologic inhibitor of TGF-beta receptor types I and II kinases, resulted in increased CAR RNA and protein levels as well as improved infectability with adenovirus. This was observed in cells induced to undergo EMT by addition of exogenous TGF-beta and in those that were transformed by endogenous autocrine/paracrine TGF-beta. These findings show down-regulation of CAR in the context of EMT and suggest that combination of therapeutic adenoviruses and TGF-beta receptor inhibitors could be an efficient anticancer strategy.

KW - Adenoviridae

KW - Animals

KW - Carcinoma

KW - Coxsackie and Adenovirus Receptor-Like Membrane Protein

KW - Cricetinae

KW - Epithelial Cells

KW - Female

KW - Humans

KW - Mammary Neoplasms, Experimental

KW - Mesoderm

KW - Mice

KW - Phosphatidylinositol 3-Kinases

KW - Receptors, Transforming Growth Factor beta

KW - Receptors, Virus

KW - Skin Neoplasms

KW - Transcription, Genetic

KW - Transforming Growth Factor beta

KW - Up-Regulation

U2 - 10.1158/0008-5472.CAN-05-2328

DO - 10.1158/0008-5472.CAN-05-2328

M3 - SCORING: Journal article

C2 - 16452224

VL - 66

SP - 1648

EP - 1657

JO - CANCER RES

JF - CANCER RES

SN - 0008-5472

IS - 3

ER -