The Emerging Role of SOX2 in Cell Proliferation and Survival and Its Crosstalk with Oncogenic Signaling in Lung Cancer
| Autor: | Chien Tsun Chen, Yu-Ting Chou, Yau-Huei Wei, Sheng Chieh Lin, Chih Chan Lee, Cheng-Wen Wu, Chih Hung Chung, Chi Hsiu Chung, Yu Rong Kao, Sey En Lin, Yuan Hung Wang, Shih Hsin Hsiao |
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| Rok vydání: | 2013 |
| Předmět: |
Lung Neoplasms
Paclitaxel Cellular differentiation bcl-X Protein Apoptosis Cell Growth Processes Mice stomatognathic system SOX2 Cancer stem cell Cell Line Tumor Autophagy medicine Animals Humans Gene Silencing Epidermal growth factor receptor Progenitor cell Lung cancer biology Cell growth SOXB1 Transcription Factors fungi Cell Biology medicine.disease Survival Analysis Cell biology ErbB Receptors Drug Resistance Neoplasm Gene Knockdown Techniques embryonic structures Cancer research biology.protein Heterografts Molecular Medicine Ectopic expression sense organs Cisplatin biological phenomena cell phenomena and immunity Signal Transduction Developmental Biology |
| Zdroj: | Stem Cells. 31:2607-2619 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.1518 |
| Popis: | Tumor cells have long been observed to share several biological characteristics with normal stem/progenitor cells; however, the oncogenic mechanisms underlying the lung stem/progenitor cell signaling remain elusive. Here, we report that SOX2, a self-renewal factor in lung stem/progenitor cells, is highly expressed in a subclass of lung cancer cells, the proliferation, survival, and chemoresistance of which are dependent on SOX2 signaling. Overexpression of SOX2 promotes oncogenic phenotypes in lung cancer cells; knockdown of SOX2 attenuated cell proliferation. We observed that SOX2 increased the expression of epidermal growth factor receptor (EGFR), and EGFR activation further upregulated SOX2 levels, forming a positive feedback loop. SOX2 expression promoted chemoresistance, and silencing of SOX2 perturbed mitochondrial function, causing marked apoptosis and autophagy. SOX2 induced BCL2L1, the ectopic expression of which rescued the effects of SOX2 silencing on apoptosis, autophagy, and mitochondrial function. SOX2 promoted tumor formation, along with increased cell proliferation in a xenograft mouse model. SOX2 expression is associated with poor prognosis in lung cancer patients; moreover, SOX2, EGFR, and BCL2L1 expression levels were significantly correlated in lung tumors. Our findings support the emerging role of SOX2 in cell proliferation and survival by eliciting oncogenic EGFR and BCL2L1 signaling with potential applications as a prognosis marker and a therapeutic target in lung cancer. Stem Cells 2013;31:2607–2619 |
| Databáze: | OpenAIRE |
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