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Life or Death Decisions: The Epithelial-Mesenchymal Transition in Cancer and Metastasis

Life or Death Decisions
Reported by
Catherine Zandonella

Posted March 21, 2008


The transition of an epithelial cell into a mesenchymal cell is a fundamental step in embryonic development and organ formation. Epithelial cells typically grow in a sheet of uniformly spaced cells that are held tightly to each other by adhesion molecules. These cells line the surfaces of structures throughout the body. Mesenchymal cells, in contrast, grow in non-uniform sizes and shapes and are not tightly adhered to each other. This enables them to migrate. Connective tissues, smooth muscle, and vascular endothelium are all derived from mesenchymal cells.

The conversion of cells from epithelial to mesenchymal states thus makes migration possible, a necessary step in embryonic development. However, this life-giving transition also enables cancer cell metastasis. Understanding the epithelial-mesenchymal transition could therefore lead to new therapies for the prevention of metastases. Researchers gathered at the Academy on January 24, 2008, to present their research on the biology of the epithelial-mesenchymal transition.

J. Silvio Gutkind

Dorsam RT, Gutkind JS. 2007. G-protein-coupled receptors and cancer. Nat. Rev. Cancer 7: 79-94.

Gavard J, Patel V, Gutkind JS. 2008. Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev. Cell 14: 25-36.

Gavard J, Gutkind JS. 2006. VEGF controls endothelial-cell permeability by promoting the β-arrestin-dependent endocytosis of VE-cadherin. Nat. Cell Biol. 8: 1223-1234.

Patel V, Rosenfeldt HM, Lyons R, et al. 2007. Persistent activation of Rac1 in squamous carcinomas of the head and neck: evidence for an EGFR/Vav2 signaling axis involved in cell invasion. Carcinogenesis 28: 1145-1152.

Rosenfeldt H, Castellone MD, Randazzo PA, Gutkind JS. 2006. Rac inhibits thrombin-induced Rho activation: evidence of a Pak-dependent GTPase crosstalk. J. Mol. Signal. Dec 6; 1:8. Full Text

Tan W, Palmby TR, Gavard J, et al. 2008. An essential role for Rac1 in endothelial cell function and vascular development. FASEB J. Feb 1; [Epub ahead of print]

Zhou G, Xie TX, Zhao M, et al. 2008. Reciprocal negative regulation between S100A7/psoriasin and β-catenin signaling plays an important role in tumor progression of squamous cell carcinoma of oral cavity. Oncogene Jan 28; [Epub ahead of print]

Jiri Zavadil

Blumenberg M, Gao S, Dickman K, et al. 2007. Chromatin structure regulation in transforming growth factor-β-directed epithelial-mesenchymal transition. Cells Tissues Organs 185: 162-174.

Zavadil J, Bitzer M, Liang D, et al. 2001. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc. Natl. Acad. Sci. USA 98: 6686-6691. Full Text

Zavadil J, Böttinger EP. 2005. TGF-β and epithelial-to-mesenchymal transitions. Oncogene 24: 5764-5774. (PDF, 176 KB) Full Text

Zavadil J, Cermak L, Soto-Nieves N, Böttinger EP. 2004. Integration of TGF-β/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J. 23: 1155-1165. (PDF, 390 KB) Full Text

Zavadil J, Narasimhan M, Blumenberg M, Schneider RJ. 2007. Transforming growth factor-β and microRNA:mRNA regulatory networks in epithelial plasticity. Cells Tissues Organs 185: 157-161.


Denise Montell, PhD

Johns Hopkins University School of Medicine
e-mail | web site | publications

Denise Montell completed her PhD in neurosciences at Stanford University in 1988, under the guidance of Corey Goodman. She went on to do postdoctoral work with Allan Spradling at the Carnegie Institution of Washington. In 1990 she moved into an independent "Staff Associate" position at the Carnegie. Since 1992 she has been a faculty member in the Department of Biological Chemistry at the Johns Hopkins University School of Medicine, where she is currently a full professor and director of the Graduate Program in Biological Chemistry.

J. Silvio Gutkind, PhD

National Institute of Dental and Craniofacial Research, NIH
e-mail | web site | publications

Silvio Gutkind is chief of the Oral and Pharyngeal Cancer Branch as well as the Cell Growth Regulation Section and Molecular Carcinogenesis Unit at the National Institute of Dental and Craniofacial Research. He studies the molecular basis of signal transduction in cell proliferation, differentiation, and neoplastic transformation and is using this knowledge to develop molecular markers of disease progression and novel therapeutic approaches for oral malignancies. Gutkind completed a PhD in pharmacy and Biochemistry at the University of Buenos Aires, Argentina. Before joining the NIDCR in 1988, he held fellowships at the National Institute of Mental Health and the National Cancer Institute.

Jiri Zavadil, PhD

New York University School of Medicine
e-mail | web site | publications

Jiri Zavadil is assistant professor in the Department of Pathology at the New York University School of Medicine. Among his projects, he has been focusing on the role of TGF-β in the epithelial-mesenchymal transition. He completed his PhD at the Charles University in Prague, Czech Republic and obtained his postdoctoral training at the Albert Einstein College of Medicine of the Yeshiva University in New York, where he was a fellow of the American Association for Cancer Research-Sidney Kimmel Foundation.

Catherine Zandonella

Catherine Zandonella is a science writer based in New York City, covering such topics as environmental science, public health, and applied technology. She has a master's degree in public health from the University of California, Berkeley. Zandonella has written for a number of publications, including New Scientist, The Scientist, and Nature.

Cancer and Signaling Discussion Group