Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions
| Autor: | Neil W. Gibson, David Epstein, Maryland Rosenfeld-Franklin, Mark Miglarese, Izabela Sujka-Kwok, Alexandra Eyzaguirre, Kenneth K. Iwata, Filippo Petti, Elizabeth Buck, Sharon Barr, John D. Haley, Stuart Thomson, Suzanne Russo |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty PDGFR EGFR Biology Epithelium Receptor tyrosine kinase Metastasis Mesoderm medicine Animals Humans Vimentin Neoplasm Invasiveness Neoplastic transformation Epithelial–mesenchymal transition Epidermal growth factor receptor Twist Autocrine signalling Cancer EGFR inhibitors Zeb-1 Carcinoma EMT E-cadherin Cell migration General Medicine ErbB Receptors Epithelial-to-mesenchymal transition Erlotinib Snail Oncology biology.protein Cancer research Cyclin-dependent kinase 8 Original Article IGF-1R |
| Zdroj: | Clinical & Experimental Metastasis |
| ISSN: | 1573-7276 0262-0898 |
| DOI: | 10.1007/s10585-007-9121-7 |
| Popis: | Over 90% of all cancers are carcinomas, malignancies derived from cells of epithelial origin. As carcinomas progress, these tumors may lose epithelial morphology and acquire mesenchymal characteristics which contribute to metastatic potential. An epithelial-to-mesenchymal transition (EMT) similar to the process critical for embryonic development is thought to be an important mechanism for promoting cancer invasion and metastasis. Epithelial-to-mesenchymal transitions have been induced in vitro by transient or unregulated activation of receptor tyrosine kinase signaling pathways, oncogene signaling and disruption of homotypic cell adhesion. These cellular models attempt to mimic the complexity of human carcinomas which respond to autocrine and paracrine signals from both the tumor and its microenvironment. Activation of the epidermal growth factor receptor (EGFR) has been implicated in the neoplastic transformation of solid tumors and overexpression of EGFR has been shown to correlate with poor survival. Notably, epithelial tumor cells have been shown to be significantly more sensitive to EGFR inhibitors than tumor cells which have undergone an EMT-like transition and acquired mesenchymal characteristics, including non-small cell lung (NSCLC), head and neck (HN), bladder, colorectal, pancreas and breast carcinomas. EGFR blockade has also been shown to inhibit cellular migration, suggesting a role for EGFR inhibitors in the control of metastasis. The interaction between EGFR and the multiple signaling nodes which regulate EMT suggest that the combination of an EGFR inhibitor and other molecular targeted agents may offer a novel approach to controlling metastasis. |
| Databáze: | OpenAIRE |
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