Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma

被引：226
作者：
Chen, Demeng [1 ,2 ]
Wu, Mansi [1 ,2 ]
Li, Yang [1 ,2 ]
Chang, Insoon [1 ,2 ]
Yuan, Quan [1 ,2 ]
Ekimyan-Salvo, Mari [1 ,2 ]
Deng, Peng [1 ,2 ]
Yu, Bo [1 ,2 ]
Yu, Yongxin [1 ,2 ]
Dong, Jiaqiang [1 ,2 ]
Szymanski, John M. [1 ,2 ]
Ramadoss, Sivakumar [1 ,2 ]
Li, Jiong [1 ,2 ]
Wang, Cun-Yu [1 ,2 ,3 ]
机构：
[1] UCLA, Jonsson Comprehens Canc Ctr, Sch Dent, Div Oral Biol & Med,Lab Mol Signaling, Los Angeles, CA 90095 USA
[2] UCLA, Broad Stem Cell Res Ctr, Los Angeles, CA 90095 USA
[3] UCLA, Henry Samueli Sch Engn & Appl Sci, Dept Bioengn, Los Angeles, CA 90095 USA
来源：
CELL STEM CELL | 2017年 / 20卷 / 05期
关键词：
SELF-RENEWAL; TUMOR-GROWTH; HEAD; IDENTIFICATION; PROMOTES; BMI-1; HETEROGENEITY; PLASTICITY; PREVENTS; ANOIKIS;
D O I：
10.1016/j.stem.2017.02.003
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
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.
引用
收藏
页码：621 / +
页数：20
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