TY - JOUR
T1 - Epithelial Mesenchymal Transition in Tumor Metastasis
AU - Mittal, Vivek
N1 - Funding Information:
The author thanks Sharrell Lee for editing this manuscript and members of the author’s laboratory for providing comments on the manuscript. The author also thanks Dr. Thomas Brabletz (University of Erlangen-Nuernberg, Germany) for comments on the figure describing key milestones for EMT in cancer research. The author is supported by grants from the National Institutes of Health and Department of Defense. The author apologizes for being unable to include several excellent studies due to space limitations.
Publisher Copyright:
© 2018 by Annual Reviews. All rights reserved.
PY - 2018/1/24
Y1 - 2018/1/24
N2 - Metastasis is the major cause of cancer-related deaths; therefore, the prevention and treatment of metastasis are fundamental to improving clinical outcomes. Epithelial mesenchymal transition (EMT), an evolutionarily conserved developmental program, has been implicated in carcinogenesis and confers metastatic properties upon cancer cells by enhancing mobility, invasion, and resistance to apoptotic stimuli. Furthermore, EMT-derived tumor cells acquire stem cell properties and exhibit marked therapeutic resistance. Given these attributes, the complex biological process of EMT has been heralded as a key hallmark of carcinogenesis, and targeting EMT pathways constitutes an attractive strategy for cancer treatment. However, demonstrating the necessity of EMT for metastasis in vivo has been technically challenging, and recent efforts to demonstrate a functional contribution of EMT to metastasis have yielded unexpected results. Therefore, determining the functional role of EMT in metastasis remains an area of active investigation. Studies using improved lineage tracing systems, dynamic in vivo imaging, and clinically relevant in vivo models have the potential to uncover the direct link between EMT and metastasis. This review focuses primarily on recent advances in and emerging concepts of the biology of EMT in metastasis in vivo and discusses future directions in the context of novel diagnostic and therapeutic opportunities.
AB - Metastasis is the major cause of cancer-related deaths; therefore, the prevention and treatment of metastasis are fundamental to improving clinical outcomes. Epithelial mesenchymal transition (EMT), an evolutionarily conserved developmental program, has been implicated in carcinogenesis and confers metastatic properties upon cancer cells by enhancing mobility, invasion, and resistance to apoptotic stimuli. Furthermore, EMT-derived tumor cells acquire stem cell properties and exhibit marked therapeutic resistance. Given these attributes, the complex biological process of EMT has been heralded as a key hallmark of carcinogenesis, and targeting EMT pathways constitutes an attractive strategy for cancer treatment. However, demonstrating the necessity of EMT for metastasis in vivo has been technically challenging, and recent efforts to demonstrate a functional contribution of EMT to metastasis have yielded unexpected results. Therefore, determining the functional role of EMT in metastasis remains an area of active investigation. Studies using improved lineage tracing systems, dynamic in vivo imaging, and clinically relevant in vivo models have the potential to uncover the direct link between EMT and metastasis. This review focuses primarily on recent advances in and emerging concepts of the biology of EMT in metastasis in vivo and discusses future directions in the context of novel diagnostic and therapeutic opportunities.
KW - Cancer stem cells
KW - Collective migration
KW - Epithelial mesenchymal transition
KW - Lineage tracing
KW - Metastasis
KW - MiRNA
KW - Resistance
KW - Therapy
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U2 - 10.1146/annurev-pathol-020117-043854
DO - 10.1146/annurev-pathol-020117-043854
M3 - Article
C2 - 29414248
AN - SCOPUS:85041731275
SN - 1553-4006
VL - 13
SP - 395
EP - 412
JO - Annual Review of Pathology: Mechanisms of Disease
JF - Annual Review of Pathology: Mechanisms of Disease
ER -