The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
A Twist-Snail Axis Critical for TrkB-Induced Epithelial-Mesenchymal Transition-Like Transformation, Anoikis Resistance, and Metastasis
Open accessAbstract
In a genomewide anoikis suppression screen for metastasis genes, we previously identified the neurotrophic receptor tyrosine kinase TrkB. In mouse xenografts, activated TrkB caused highly invasive and metastatic tumors. Here, we describe that TrkB also induces a strong morphological transformation, resembling epithelial-mesenchymal transition (EMT). This required TrkB kinase activity, a functional mitogen-activated protein kinase pathway, suppression of E-cadherin, and induction of Twist, a transcription factor contributing to EMT and metastasis. RNA interference (RNAi)-mediated Twist depletion blocked TrkB-induced EMT-like transformation, anoikis suppression, and growth of tumor xenografts. By searching for essential effectors of TrkB-Twist signaling, we found that Twist induces Snail, another EMT regulator associated with poor cancer prognosis. Snail depletion impaired EMT-like transformation and anoikis suppression induced by TrkB, but in contrast to Twist depletion, it failed to inhibit tumor growth. Instead, Snail RNAi specifically impaired the formation of lung metastases. Epistasis experiments suggested that Twist acts upstream from Snail. Our results demonstrate that TrkB signaling activates a Twist-Snail axis that is critically involved in EMT-like transformation, tumorigenesis, and metastasis. Moreover, our data shed more light on the epistatic relationship between Twist and Snail, two key transcriptional regulators of EMT and metastasis.
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Cites
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Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
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Trk Receptors: Roles in Neuronal Signal Transduction
Huang, E. J., & Reichardt, L. F. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161629 · Cited by 2,537 · cited 1×
“Several canonical signal transduction pathways are stimulated by TrkB, including the MAPK pathway, PI3K pathway, and RAC1 GTPase signaling (37, 51).”
BackgroundThe snail superfamily of zinc-finger transcription factors
Nieto, M. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm757 · Cited by 1,719
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Mice lacking brain-derived neurotrophic factor develop with sensory deficits
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The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901
Barrett, S. D., Bridges, A. J., Dudley, D. T., Saltiel, A. R., Fergus, J. H., Flamme, C. M., Delaney, A. M., Kaufman, M., LePage, S., Leopold, W. R., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.10.054 · Cited by 289
Cited by
Anoikis molecular pathways and its role in cancer progression
Paoli, P., Giannoni, E., & Chiarugi, P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.026 · Cited by 1,160
EMT as the ultimate survival mechanism of cancer cells
Tiwari, N., Gheldof, A., Tatari, M., & Christofori, G. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.02.013 · Cited by 512
Zhang, J., Tian, X.-J., Zhang, H., Teng, Y., Li, R., Bai, F., Elankumaran, S., & Xing, J. (2014) · Science Signaling · doi:10.1126/scisignal.2005304 · Cited by 462
Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression
Buchheit, C. L., Weigel, K. J., & Schafer, Z. T. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3789 · Cited by 367
Mechanisms that link the oncogenic epithelial–mesenchymal transition to suppression of anoikis
Frisch, S. M., Schaller, M., & Cieply, B. (2013) · Journal of Cell Science · doi:10.1242/jcs.120907 · Cited by 295
Metadata
- Authors
- Smit, M. A., Geiger, T. R., Song, J.-Y., Gitelman, I., & Peeper, D. S.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2009-07-01
- Volume
- 29
- Issue
- 13
- Pages
- 3722-3737
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2116983313
- Cited by
- 218
- References
- 8
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Smit, M. A., Geiger, T. R., Song, J.-Y., Gitelman, I., & Peeper, D. S. (2009). A Twist-Snail Axis Critical for TrkB-Induced Epithelial-Mesenchymal Transition-Like Transformation, Anoikis Resistance, and Metastasis. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.01164-08
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