Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?
Abstract
:1. Introduction
2. EMT Involvement in Cancer Cell Dissemination
- (1)
- Detachment from the highly-organized epithelial layer; this requires reducing cell-cell contacts and rearranging the cytoskeletal architecture, in favor of a motile phenotype;
- (2)
- Impairment of the integrity of the basement membrane through active proteolysis, and then invasion of the surrounding stroma as strands or cords. Once in the tumor stroma, cells can efficiently cross-talk with multiple mesenchymal and inflammatory cell types, which in turn support their invasiveness;
- (3)
- Dissemination at distance through the lymphatic and/or hematogenous circulation, taking advantage of the leaky neovasculature arising in the tumor microenvironment; and
- (4)
3. Evidence for EMT in Human Carcinomas
4. Expression of EMT Features in CCA and Underlying Mechanisms Involved
4.1. Cytokines, Growth Factors and Morphogens Promoting EMT
EMT Inducer | References |
---|---|
Inflammatory cyto/chemokines | |
TGF-β1 | [55,56,57,58] |
TNF-α | [59] |
IL-6 | [60] |
HMGB1 | [61] |
SDF-1 | [50] |
Growth factors | |
EGF | [62,63] |
FGF-19 | [64] |
Morphogens | |
Notch1/Sox9 | [65,66,67] |
Sonic Hh | [68] |
4.2. miRNAs Promoting EMT
4.3. Oncogenes and Tumor Suppressor Genes Regulating EMT
4.4. Disease Mechanisms Inducting the “Transitional” Phenotype
5. EMT and CAFs Generation: Insights from CCA
6. CCA as Model to Redefine the Concept of EMT in Cancer Invasiveness
7. Conclusions
Acknowledgments
Conflicts of Interest
References
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Brivio, S.; Cadamuro, M.; Fabris, L.; Strazzabosco, M. Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma? J. Clin. Med. 2015, 4, 2028-2041. https://doi.org/10.3390/jcm4121958
Brivio S, Cadamuro M, Fabris L, Strazzabosco M. Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma? Journal of Clinical Medicine. 2015; 4(12):2028-2041. https://doi.org/10.3390/jcm4121958
Chicago/Turabian StyleBrivio, Simone, Massimiliano Cadamuro, Luca Fabris, and Mario Strazzabosco. 2015. "Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?" Journal of Clinical Medicine 4, no. 12: 2028-2041. https://doi.org/10.3390/jcm4121958