Int J Biochem Mol Biol 2012;3(2):117-136
Review Article
Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic
behavior of epithelial malignancies
Lindsay J Talbot, Syamal D Bhattacharya, Paul C Kuo
Department of Surgery, Loyola University Medical Center, Maywood, IL; Department of Surgery, Duke University Medical Center, Durham, NC;
Department of Molecular Pharmacology and Therapeutics, Loyola University Medical Center, Maywood, IL
Received March 19, 2012; accepted April 2, 2012; Epub May 18, 2012; Published June 15, 2012
Abstract: Objective: The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for
metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer
metastasis. Summary Background Data: Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and
baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology
program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular
components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. Methods: A
literature review was performed using PubMed for “epithelial-mesenchymal transition”, “tumor microenvironment”, “TGF-β and cancer”, “Wnt
and epithelial-mesenchymal transition”, “Notch and epithelial-mesenchymal transition”, “Hedgehog and epithelial-mesenchymal transition”
and “hypoxia and metastasis”. Relevant primary studies and review articles were assessed. Results: Major signaling pathways involved in
epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription
factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide
crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in
epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining
metastatic potential. Conclusions: While the mechanisms promoting metastasis are extremely wide ranging and still under intense
investigation, the epithelial-mesenchymal transition program and the tumor microenvironment are both critically involved in the acquisition of
metastatic potential. As our understanding of these complexities increases, the ability to target these processes for therapy will offer new
promise in the treatment of epithelial malignancy and metastasis. (IJBMB1203006)
Keywords: epithelial-mesenchymal transition, tumor microenvironment, metastasis, prevention, therapy
Address all correspondence to:
Dr. Paul C Kuo
Loyola University Medical Center
2160 South First Ave, EMS Bldg, Rm 3244
Maywood, IL 60153, USA.
Tel: 708-327-2710; Fax: 708-327-2852
E-mail: pkuo@lumc.edu
Review Article
Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic
behavior of epithelial malignancies
Lindsay J Talbot, Syamal D Bhattacharya, Paul C Kuo
Department of Surgery, Loyola University Medical Center, Maywood, IL; Department of Surgery, Duke University Medical Center, Durham, NC;
Department of Molecular Pharmacology and Therapeutics, Loyola University Medical Center, Maywood, IL
Received March 19, 2012; accepted April 2, 2012; Epub May 18, 2012; Published June 15, 2012
Abstract: Objective: The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for
metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer
metastasis. Summary Background Data: Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and
baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology
program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular
components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. Methods: A
literature review was performed using PubMed for “epithelial-mesenchymal transition”, “tumor microenvironment”, “TGF-β and cancer”, “Wnt
and epithelial-mesenchymal transition”, “Notch and epithelial-mesenchymal transition”, “Hedgehog and epithelial-mesenchymal transition”
and “hypoxia and metastasis”. Relevant primary studies and review articles were assessed. Results: Major signaling pathways involved in
epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription
factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide
crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in
epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining
metastatic potential. Conclusions: While the mechanisms promoting metastasis are extremely wide ranging and still under intense
investigation, the epithelial-mesenchymal transition program and the tumor microenvironment are both critically involved in the acquisition of
metastatic potential. As our understanding of these complexities increases, the ability to target these processes for therapy will offer new
promise in the treatment of epithelial malignancy and metastasis. (IJBMB1203006)
Keywords: epithelial-mesenchymal transition, tumor microenvironment, metastasis, prevention, therapy
Address all correspondence to:
Dr. Paul C Kuo
Loyola University Medical Center
2160 South First Ave, EMS Bldg, Rm 3244
Maywood, IL 60153, USA.
Tel: 708-327-2710; Fax: 708-327-2852
E-mail: pkuo@lumc.edu
 |  |  |  |  |  |  |