Cigarette smoking promotes keratinocyte malignancy via generation of cancer stem-like cells
| Autor: | Li Xiufeng, Xiuyun Lin, Xing Liu, Yiqing Zheng, Yuanzhong Chen, Lin Shuchun, Jin Rong, Tao Zeng, Jieming Xie, Jizhen Lin, Wenfeng Mei, Haichun Lai, Qiong Zhang, Xiong Jiani, Hu Xiaohua, Huanjiao Weng, Jianbo Yang, Shubin Fang, Yunlu Xu |
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| Rok vydání: | 2021 |
| Předmět: |
keratinocytes
cancer stem-like cells cigarette smoking head and neck squamous cell carcinoma medicine.disease_cause B lymphoma Mo-MLV insertion region 1 homolog 03 medical and health sciences 0302 clinical medicine In vivo octamer-binding transcription factor-4 Medicine 030212 general & internal medicine Transcription factor Gene knockdown business.industry Cancer medicine.disease Head and neck squamous-cell carcinoma medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Signal transduction business Carcinogenesis Keratinocyte Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | Objectives: Cigarette smoking is involved in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms of cigarette smoking-induced HNSCC carcinogenesis are unclear and may involve cancer stem-like cell generation. We examined the effects of cigarette smoke condensate (CSC) on the formation of cancer stem-like cells, which are rich in octamer-binding transcription factor (OCT)-4, inhibitor of differentiation 1 (ID1), nuclear factor (NF)-κB, and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1). Materials and Methods: We used in vitro, in vivo, and archival human HNSCC tissue analysis to evaluate the effects of CSC on cancer stem-like cell formation. Results: We found that CSC regulated OCT-4 expression, which subsequently regulated ID1 and NF-κB, at the promoter, mRNA, and protein levels in vitro. Furthermore, OCT-4 knockdown with siRNA reduced ID1 expression. ID1 and NF-κB synergistically increased the expression of BMI-1 and stimulated keratinocyte sphere generation. In vivo, ID1 and NF-κB acted together to generate malignant xenograft tumors, which were aggressive locally and systemically metastatic. Clinical data confirmed that ID1- and NF-κB-positive patients had poor clinical outcomes and 5-year disease-free survival. Conclusion: Our data suggest that smoking cigarettes promoted cancer stem-like cell generation in the head and neck area via the OCT-4/ID1/NF-κB/BMI-1 signaling pathway. |
| Databáze: | OpenAIRE |
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