CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Portella, G.
Right arrow Articles by Balmain, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Portella, G.
Right arrow Articles by Balmain, A.

Cell Growth & Differentiation, Vol 9, Issue 5 393-404, Copyright © 1998 by American Association of Cancer Research


ARTICLES

Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion

G Portella, SA Cumming, J Liddell, W Cui, H Ireland, RJ Akhurst and A Balmain
Department of Medical Oncology, Glasgow University, United Kingdom.

Transforming growth factor beta1 (TGF-beta1) regulates both cell growth and cellular plasticity and is therefore important in the molecular control of both the developmental and neoplastic processes. It has been suggested that TGF-beta1 may be a positive or negative regulator of tumorigenesis. Stimulation of tumorigenesis could be due to its action as an immunosuppressor or as an inducer of angiogenesis, or by its direct action on the cell in promoting cellular plasticity. In the current study, we provide evidence that TGF-beta1 can act directly on keratinocytes in vivo to induce the reversible epithelial-mesenchymal conversion of a malignant metastatic keratinocyte cell line. Two squamous clones from the cell line were shown to undergo a reversible conversion to a fibroblastoid phenotype after culture in 1 ng/ml TGF-beta1. The morphological conversion became apparent at 24 h post-TGF-beta treatment and was complete after another 24 h. The conversion was characterized by a rapid delocalization of E-cadherin within 6-12 h posttreatment, followed by down-regulation of E-cadherin levels by 72 h. These squamous clones spontaneously converted to a fibroblastoid phenotype after s.c. injection in nude mice. Importantly, four of four clones that had been stably transfected with a dominant negative TGF-beta type II receptor were unable to undergo this mesenchymal switch in vivo, despite the fact that all clones stably transfected with neomyocin resistance alone retained their spindle characteristics in vivo. This demonstrates that the epithelial-mesenchymal conversion event is mediated directly via the TGF-beta signaling pathway of the tumor cell per se, and that it is sufficient to significantly enhance tumorigenicity and the malignant and invasive characteristics of the tumor in vivo.


This article has been cited by other articles:


Home page
Cold Spring Harb. Perspect. Biol.Home page
R. J. Akhurst
Targeting TGF-{beta} Signaling for Therapeutic Gain
Cold Spring Harb Perspect Biol, October 1, 2017; 9(10): a022301 - a022301.
[Abstract] [Full Text] [PDF]


Home page
Biochm. Soc. Trans.Home page
J. J. Huang and G. C. Blobe
Dichotomous roles of TGF-{beta} in human cancer
Biochm. Soc. Trans., October 15, 2016; 44(5): 1441 - 1454.
[Abstract] [Full Text] [PDF]


Home page
Physiol. GenomicsHome page
T. N. Beck, A. J. Chikwem, N. R. Solanki, and E. A. Golemis
Bioinformatic approaches to augment study of epithelial-to-mesenchymal transition in lung cancer
Physiol Genomics, October 1, 2014; 46(19): 699 - 724.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
N. Mise, R. Savai, H. Yu, J. Schwarz, N. Kaminski, and O. Eickelberg
Zyxin Is a Transforming Growth Factor-{beta} (TGF-{beta})/Smad3 Target Gene That Regulates Lung Cancer Cell Motility via Integrin {alpha}5{beta}1
J. Biol. Chem., September 7, 2012; 287(37): 31393 - 31405.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
S. Lamouille, E. Connolly, J. W. Smyth, R. J. Akhurst, and R. Derynck
TGF-{beta}-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion
J. Cell Sci., March 1, 2012; 125(5): 1259 - 1273.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
E. C. Connolly, E. F. Saunier, D. Quigley, M. T. Luu, A. De Sapio, B. Hann, J. M. Yingling, and R. J. Akhurst
Outgrowth of Drug-Resistant Carcinomas Expressing Markers of Tumor Aggression after Long-term T{beta}RI/II Kinase Inhibition with LY2109761
Cancer Res., March 15, 2011; 71(6): 2339 - 2349.
[Abstract] [Full Text] [PDF]


Home page
Cancer Genomics ProteomicsHome page
M. PERERA, C. S. TSANG, R. J. DISTEL, J. N. LACY, L. OHNO-MACHADO, V. RICCHIUTI, L. P. SAMARANAYAKE, G. B. SMEJKAL, M. G. SMITH, A. J. TRACHTENBERG, et al.
TGF-{beta}1 Interactome: Metastasis and Beyond
Cancer Genomics Proteomics, July 1, 2010; 7(4): 217 - 229.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
E. Perez-Gomez, M. Villa-Morales, J. Santos, J. Fernandez-Piqueras, C. Gamallo, J. Dotor, C. Bernabeu, and M. Quintanilla
A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis
Cancer Res., November 1, 2007; 67(21): 10268 - 10277.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
K. L. Andarawewa, A. C. Erickson, W. S. Chou, S. V. Costes, P. Gascard, J. D. Mott, M. J. Bissell, and M. H. Barcellos-Hoff
Ionizing Radiation Predisposes Nonmalignant Human Mammary Epithelial Cells to Undergo Transforming Growth Factor {beta} Induced Epithelial to Mesenchymal Transition
Cancer Res., September 15, 2007; 67(18): 8662 - 8670.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
T. Shirakihara, M. Saitoh, and K. Miyazono
Differential Regulation of Epithelial and Mesenchymal Markers by {delta}EF1 Proteins in Epithelial Mesenchymal Transition Induced by TGF-beta
Mol. Biol. Cell, September 1, 2007; 18(9): 3533 - 3544.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. Beisner, M. B. Buck, P. Fritz, J. Dippon, M. Schwab, H. Brauch, G. Zugmaier, K. Pfizenmaier, and C. Knabbe
A Novel Functional Polymorphism in the Transforming Growth Factor-{beta}2 Gene Promoter and Tumor Progression in Breast Cancer.
Cancer Res., August 1, 2006; 66(15): 7554 - 7561.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
U. Valcourt, M. Kowanetz, H. Niimi, C.-H. Heldin, and A. Moustakas
TGF-{beta} and the Smad Signaling Pathway Support Transcriptomic Reprogramming during Epithelial-Mesenchymal Cell Transition
Mol. Biol. Cell, April 1, 2005; 16(4): 1987 - 2002.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
H. G. Munshi, Y. I. Wu, S. Mukhopadhyay, A. J. Ottaviano, A. Sassano, J. E. Koblinski, L. C. Platanias, and M. S. Stack
Differential Regulation of Membrane Type 1-Matrix Metalloproteinase Activity by ERK 1/2- and p38 MAPK-modulated Tissue Inhibitor of Metalloproteinases 2 Expression Controls Transforming Growth Factor-{beta}1-induced Pericellular Collagenolysis
J. Biol. Chem., September 10, 2004; 279(37): 39042 - 39050.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
P.-L. So, K. Lee, J. Hebert, P. Walker, Y. Lu, J. Hwang, L. Kopelovich, M. Athar, D. Bickers, M. Aszterbaum, et al.
Topical Tazarotene Chemoprevention Reduces Basal Cell Carcinoma Number and Size in Ptch1+/- Mice Exposed to Ultraviolet or Ionizing Radiation
Cancer Res., July 1, 2004; 64(13): 4385 - 4389.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
R. L. de Cicco, J. C. Watson, D. E. Bassi, S. Litwin, and A. J. Klein-Szanto
Simultaneous Expression of Furin and Vascular Endothelial Growth Factor in Human Oral Tongue Squamous Cell Carcinoma Progression
Clin. Cancer Res., July 1, 2004; 10(13): 4480 - 4488.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. E. Seton-Rogers, Y. Lu, L. M. Hines, M. Koundinya, J. LaBaer, S. K. Muthuswamy, and J. S. Brugge
Cooperation of the ErbB2 receptor and transforming growth factor {beta} in induction of migration and invasion in mammary epithelial cells
PNAS, February 3, 2004; 101(5): 1257 - 1262.
[Abstract] [Full Text] [PDF]


Home page
DevelopmentHome page
W. Li, W. Qiao, L. Chen, X. Xu, X. Yang, D. Li, C. Li, S. G. Brodie, M. M. Meguid, L. Hennighausen, et al.
Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in Smad4/Dpc4 conditional knockout mice
Development, December 15, 2003; 130(24): 6143 - 6153.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
R. S. Muraoka, Y. Koh, L. R. Roebuck, M. E. Sanders, D. Brantley-Sieders, A. E. Gorska, H. L. Moses, and C. L. Arteaga
Increased Malignancy of Neu-Induced Mammary Tumors Overexpressing Active Transforming Growth Factor {beta}1
Mol. Cell. Biol., December 1, 2003; 23(23): 8691 - 8703.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
C. C. Park, R. L. Henshall-Powell, A. C. Erickson, R. Talhouk, B. Parvin, M. J. Bissell, and M. H. Barcellos-Hoff
Ionizing radiation induces heritable disruption of epithelial cell interactions
PNAS, September 16, 2003; 100(19): 10728 - 10733.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
P. M. Siegel, W. Shu, R. D. Cardiff, W. J. Muller, and J. Massague
Transforming growth factor {beta} signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis
PNAS, July 8, 2003; 100(14): 8430 - 8435.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
H. Peinado, M. Quintanilla, and A. Cano
Transforming Growth Factor {beta}-1 Induces Snail Transcription Factor in Epithelial Cell Lines: MECHANISMS FOR EPITHELIAL MESENCHYMAL TRANSITIONS
J. Biol. Chem., May 30, 2003; 278(23): 21113 - 21123.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
R. C. Bates and A. M. Mercurio
Tumor Necrosis Factor-{alpha} Stimulates the Epithelial-to-Mesenchymal Transition of Human Colonic Organoids
Mol. Biol. Cell, May 1, 2003; 14(5): 1790 - 1800.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
N. Dumont, A. V. Bakin, and C. L. Arteaga
Autocrine Transforming Growth Factor-{beta} Signaling Mediates Smad-independent Motility in Human Cancer Cells
J. Biol. Chem., January 31, 2003; 278(5): 3275 - 3285.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
E. P. Bottinger and M. Bitzer
TGF-{beta} Signaling in Renal Disease
J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2600 - 2610.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
E. Psichari, A. Balmain, D. Plows, V. Zoumpourlis, and A. Pintzas
High Activity of Serum Response Factor in the Mesenchymal Transition of Epithelial Tumor Cells Is Regulated by RhoA Signaling
J. Biol. Chem., August 16, 2002; 277(33): 29490 - 29495.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
A. V. Bakin, C. Rinehart, A. K. Tomlinson, and C. L. Arteaga
p38 mitogen-activated protein kinase is required for TGF{beta}-mediatedfibroblastic transdifferentiation and cell migration
J. Cell Sci., August 1, 2002; 115(15): 3193 - 3206.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
L. Van Aelst and M. Symons
Role of Rho family GTPases in epithelial morphogenesis
Genes & Dev., May 1, 2002; 16(9): 1032 - 1054.
[Full Text] [PDF]


Home page
J. Cell Sci.Home page
J. Gotzmann, H. Huber, C. Thallinger, M. Wolschek, B. Jansen, R. Schulte-Hermann, H. Beug, and W. Mikulits
Hepatocytes convert to a fibroblastoid phenotype through the cooperation of TGF-{beta}1 and Ha-Ras: steps towards invasiveness
J. Cell Sci., March 15, 2002; 115(6): 1189 - 1202.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
M. A. Rowland-Goldsmith, H. Maruyama, K. Matsuda, T. Idezawa, M. Ralli, S. Ralli, and M. Korc
Soluble Type II Transforming Growth Factor-{beta} Receptor Attenuates Expression of Metastasis-associated Genes and Suppresses Pancreatic Cancer Cell Metastasis
Mol. Cancer Ther., January 1, 2002; 1(3): 161 - 167.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
I. Shin, A. V. Bakin, U. Rodeck, A. Brunet, and C. L. Arteaga
Transforming Growth Factor beta Enhances Epithelial Cell Survival via Akt-dependent Regulation of FKHRL1
Mol. Biol. Cell, November 1, 2001; 12(11): 3328 - 3339.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. A. Rowland-Goldsmith, H. Maruyama, T. Kusama, S. Ralli, and M. Korc
Soluble Type II Transforming Growth Factor-{beta} (TGF-{beta}) Receptor Inhibits TGF-{beta} Signaling in COLO-357 Pancreatic Cancer Cells in Vitro and Attenuates Tumor Formation
Clin. Cancer Res., September 1, 2001; 7(9): 2931 - 2940.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
D. L. Hulboy, L. M. Matrisian, and H. C. Crawford
Loss of JunB Activity Enhances Stromelysin 1 Expression in a Model of the Epithelial-to-Mesenchymal Transition of Mouse Skin Tumors
Mol. Cell. Biol., August 15, 2001; 21(16): 5478 - 5487.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
J. Zavadil, M. Bitzer, D. Liang, Y.-C. Yang, A. Massimi, S. Kneitz, E. Piek, and E. P. Bottinger
Genetic programs of epithelial cell plasticity directed by transforming growth factor-{beta}
PNAS, June 5, 2001; 98(12): 6686 - 6691.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
V. Ellenrieder, S. F. Hendler, W. Boeck, T. Seufferlein, A. Menke, C. Ruhland, G. Adler, and T. M. Gress
Transforming Growth Factor {beta}1 Treatment Leads to an Epithelial-Mesenchymal Transdifferentiation of Pancreatic Cancer Cells Requiring Extracellular Signal-regulated Kinase 2 Activation
Cancer Res., May 1, 2001; 61(10): 4222 - 4228.
[Abstract] [Full Text]


Home page
Mol. Biol. CellHome page
N. A. Bhowmick, M. Ghiassi, A. Bakin, M. Aakre, C. A. Lundquist, M. E. Engel, C. L. Arteaga, and H. L. Moses
Transforming Growth Factor-{beta}1 Mediates Epithelial to Mesenchymal Transdifferentiation through a RhoA-dependent Mechanism
Mol. Biol. Cell, January 1, 2001; 12(1): 27 - 36.
[Abstract] [Full Text]


Home page
Biol. Reprod.Home page
N. H. Machell, O. W. Blaschuk, and R. Farookhi
Developmental Expression and Distribution of N- and E-Cadherin in the Rat Ovary
Biol Reprod, September 1, 2000; 63(3): 797 - 804.
[Abstract] [Full Text]


Home page
J. Virol.Home page
I. Ganly, V. Mautner, and A. Balmain
Productive Replication of Human Adenoviruses in Mouse Epidermal Cells
J. Virol., March 15, 2000; 74(6): 2895 - 2899.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
E. Piek, A. Moustakas, A. Kurisaki, C. H. Heldin, and P. t. Dijke
TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells
J. Cell Sci., December 15, 1999; 112(24): 4557 - 4568.
[Abstract] [PDF]


Home page
Cancer Res.Home page
B. Tang, K. de Castro, H. E. Barnes, W. T. Parks, L. Stewart, E. P. Bottinger, D. Danielpour, and L. M. Wakefield
Loss of Responsiveness to Transforming Growth Factor {beta} Induces Malignant Transformation of Nontumorigenic Rat Prostate Epithelial Cells
Cancer Res., October 1, 1999; 59(19): 4834 - 4842.
[Abstract] [Full Text] [PDF]


Home page
Cell Growth Differ.Home page
R. Montesano, J. V. Soriano, G. Hosseini, M. S. Pepper, and H. Schramek
Constitutively Active Mitogen-activated Protein Kinase Kinase MEK1 Disrupts Morphogenesis and Induces an Invasive Phenotype in Madin-Darby Canine Kidney Epithelial Cells
Cell Growth Differ., May 1, 1999; 10(5): 317 - 332.
[Abstract] [Full Text]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1998 by the American Association of Cancer Research.