| Literature DB >> 28285905 |
Demeng Chen1, Mansi Wu1, Yang Li1, Insoon Chang1, Quan Yuan1, Mari Ekimyan-Salvo1, Peng Deng1, Bo Yu1, Yongxin Yu1, Jiaqiang Dong1, John M Szymanski1, Sivakumar Ramadoss1, Jiong Li1, Cun-Yu Wang2.
Abstract
Squamous cell carcinoma in the head and neck (HNSCC) is a common yet poorly understood cancer, with adverse clinical outcomes due to treatment resistance, recurrence, and metastasis. Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified. Here we show through lineage tracing and genetic ablation that BMI1+ CSCs mediate invasive growth and cervical lymph node metastasis in a mouse model of HNSCC. This model and primary human HNSCC samples contain highly tumorigenic, invasive, and cisplatin-resistant BMI1+ CSCs, which exhibit increased AP-1 activity that drives invasive growth and metastasis of HNSCC. Inhibiting AP-1 or BMI1 sensitized tumors to cisplatin-based chemotherapy, and it eliminated lymph node metastases by targeting CSCs and the tumor bulk, suggesting potential regimens to overcome resistance to treatments and eradicate HNSCC metastasis.Entities:
Keywords: AP-1; Bmi1; cancer stem cells; chemotherapy; cisplatin resistance; head and neck squamous cell carcinoma; metastasis
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Year: 2017 PMID： 28285905 PMCID： PMC5419860 DOI： 10.1016/j.stem.2017.02.003
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633