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

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Mar 14

PMID 28285905

Citations 138

Authors

Demeng Chen

Mansi Wu

Yang Li

Insoon Chang

Quan Yuan

Mari Ekimyan-Salvo

Peng Deng

Bo Yu

Yongxin Yu

Jiaqiang Dong

John M Szymanski

Sivakumar Ramadoss

Jiong Li

Cun-Yu Wang

Affiliations

Soon will be listed here.

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.

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