The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Epithelial-to-Mesenchymal Transition and Integrin-Linked Kinase Mediate Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Hepatoma Cells
Abstract
Hepatocellular carcinoma (HCC) is associated with a poor prognosis due to late diagnoses and a lack of effective treatment options. Epidermal growth factor receptor (EGFR)–targeted therapies have been effective in other cancers. However, erlotinib and cetuximab have shown only modest efficacy in clinical trials of HCC. We examined epithelial-to-mesenchymal transition (EMT) as a determinant of sensitivity of HCC to EGFR inhibitors. A panel of 12 human hepatoma cell lines were classified as epithelial or mesenchymal based on their expression of E-cadherin and vimentin. The resulting classification correlated with a previous microarray analysis of human hepatoma cell lines whereby the mesenchymal cell lines were shown to have increased expression of genes involved in metastasis and invasion. Sensitivity to erlotinib, gefitinib, and cetuximab was assessed and the epithelial cell lines were found to be significantly more susceptible to all three agents. Analysis of the EGFR pathway showed that EMT status was independent of EGFR expression or downstream extracellular signal–regulated kinase activation and only the epithelial cell lines expressed ErbB3. Interestingly, mesenchymal cells resistant to EGFR inhibitors had increased AKT and signal transducer and activator of transcription-3 activation through elevated expression of integrin-linked kinase (ILK). Mesenchymal cell lines were therefore experimentally transformed with kinase-inactive ILK (KI-ILK) with a resulting decrease in ILK activity and activation of AKT. KI-ILK transformants showed increased sensitivity to EGFR inhibitors both in vitro and in an in vivo xenograft model. These data suggest that EMT predicts HCC sensitivity to EGFR-targeted therapies and that ILK is a novel target to overcome HCC resistance to EGFR inhibition. [Cancer Res 2008;68(7):2391–9]
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Global Cancer Statistics, 2002
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EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
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Molecular requirements for epithelial–mesenchymal transition during tumor progression
Huber, M. A., Kraut, N., & Beug, H. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.08.001 · Cited by 1,821
Epithelial–mesenchymal transitions in development and pathologies
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Cancer drug resistance: an evolving paradigm
Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3599 · Cited by 4,681
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
Self-citationSingh, A., Greninger, P., Rhodes, D., Koopman, L., Violette, S., Bardeesy, N., & Settleman, J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.022 · Cited by 841
Epithelial-mesenchymal transition in cancer development and its clinical significance
Iwatsuki, M., Mimori, K., Yokobori, T., Ishi, H., Beppu, T., Nakamori, S., Baba, H., & Mori, M. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2009.01419.x · Cited by 780
Understanding resistance to EGFR inhibitors—impact on future treatment strategies
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Metadata
- Authors
- Fuchs, B. C., Fujii, T., Dorfman, J. D., Goodwin, J. M., Zhu, A. X., Lanuti, M., & Tanabe, K. K.
- Venue
- Cancer Research
- Published
- 2008-04-01
- Volume
- 68
- Issue
- 7
- Pages
- 2391-2399
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2086702949
- Cited by
- 309
- References
- 50
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Epithelial-to-Mesenchymal Transition and Integrin-Linked Kinase Mediate Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Hepatoma Cells. https://app.cochat.ai/papers/10.1158/0008-5472.can-07-2460
- The paper
- Fuchs, B. C., Fujii, T., Dorfman, J. D., Goodwin, J. M., Zhu, A. X., Lanuti, M., & Tanabe, K. K. (2008). Epithelial-to-Mesenchymal Transition and Integrin-Linked Kinase Mediate Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Hepatoma Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-07-2460
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
