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Lung cancer is the leading cause of cancer-related mortality worldwide. The five-year survival rate is very low in lung cancer patients due to diagnosis at late stages, tumor recurrence, and drug resistance. Recent studies suggest that cancer cells with self-renewal capacity contribute to tumor growth. Identification of reliable markers for cancer stem cell populations and mechanistic understanding of associated signaling pathways and regulatory factors are critically needed to improve long-term survival. Several studies have established the expression of stem cell markers (aldehyde dehydrogenase ALDH1, glycoprotein CD44 and CD133) in lung cancer cell lines and clinical samples. Association of these stem cell markers with lung cancer and the signaling pathways (Wnt, Notch, and Hedgehog) maintaining stem cell characteristics are briefly reviewed here. Interestingly, epigenetic mechanisms and regulatory roles of transcription factors such as Sox2 and Runx family members have been shown to contribute to stem cell properties and lung cancer. Understanding mechanisms regulating “stemness” and differentiation of lung epithelial cells will lead to novel therapies for successful targeting of cancer stem cells. |
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