Sox2, an EGFR induced transcriptional factor, modulates cell growth and mesenchymal-epithelial trans-differentiation (MET) of lung cancer.
| Autor: | Chih-Chan Lee, 李志展 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Aberrant expression and function of epidermal growth factor receptor (EGFR) is reported in most lung cancer cases. Sox2, a core transcription factor regulating self-renewal of stem cells, is highly expressed in lung cancer. We discovered that EGFR and its ligands (TGF-??nand EGF) induce Sox2 expression in lung cancer. Ectopic expression of c-Myc, a key effector of EGFR signaling, induced Sox2 expression; knockdown of c-Myc decreased Sox2 level in lung cancer, suggesting that EGFR induces Sox2 via a c-Myc dependent pathway. Ectopic expression of Sox2 promoted cell proliferation and anchorage-independent cell growth; knockdown of Sox2 attenuated oncogenic properties of lung cancer. In addition, Sox2-silencing induced autophagic death of lung cancer; overexpression of Sox2 prevented cell from starvation-induced autophagy. These data demonstrates that Sox2 induces oncogenesis of lung cancer. Overexpression of Sox2 promoted tumor growth in xenograft mouse model; knockdown of Sox2 inhibited tumor formation in vivo. These results support the notion that Sox2 enhances tumorigenesis of lung cancer. Through a cDNA microarray analysis for Sox2 target genes, we identified that Sox2 regulates EGFR. Immunoblotting showed that Sox2 induced EGFR expression, suggesting that an EGFR-Sox2-EGFR positive feedback loop exist in lung cancer. In addition, ectopic expression of Sox2 in lung cancer induces mesenchymal-epithelial trans-differentiation and promotes cell-matrix adhesion. Thus, Sox2 may serve as an important effector of EGFR-mediated oncogenesis and provide a novel prognostic biomarker and therapeutic target for lung cancer. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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