Abstract 1950: SMURF1 inhibition reduces cancer stem cell-like population in head and neck squamous cell carcinoma

Abstract

Abstract Cancer stem cells (CSCs) possess capabilities for long-term survival (quiescence), self-renewal, and tumor initiation thought to be responsible for drug resistance and treatment failures for many malignancies, including head and neck squamous cell carcinoma (HNSCC). Previously, we showed that the activity of bone morphogenetic protein (BMP), a key regulator of cell differentiation, proliferation, migration, and apoptosis, is inhibited in CSC-like populations enriched from HNSCC cell lines. In contrast, the BMP signaling inhibitor SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) and CD44, a marker of CSCs, were upregulated. Objectives: In this study, we characterized the role of SMURF1 for CSC maintenance and differentiating growth and identified a population of cells regulated by SMURF1. Methods: We generated a stable knockdown of SMURF1 expression in CSC-like populations using a lentivirus delivered shRNA interference construct. Long-term colony formation and Calcein AM dye efflux assays were performed to assess CSC maintenance and differentiating growth. Results: Knockdown of SMURF1 expression by shRNA reduced viability and colony formation of CSC-like cells grown in three-dimensional culture. Furthermore, reduced SMURF1 expression diminished the number of cells capable of dye efflux and decreased CD44 expression (CD44-high) in a select cell population. Conclusion: We interpret our data to suggest that SMURF1 inhibition of BMP signaling potentiates the long-term survival of HNSCC CSCs. Reduced dye efflux and expression of CD44-high cells suggests decreased maintenance of CSC-like populations along with an increased potential for differentiating growth. Targeting SMURF1 may provide a long-term benefit for HNSCC treatment to reduce resistant CSC populations and disease recurrence. Citation Format: Ali Khammanivong, Raj Gopalakrishnan, Erin B. Dickerson. SMURF1 inhibition reduces cancer stem cell-like population in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1950. doi:10.1158/1538-7445.AM2014-1950