Abstract 5448: The role of CLCA2 in cell proliferation and survival of HNSCC—potential biomarker for sensitivity to EGFR inhibitors

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) develops in mucous membranes that line the mouth, throat and sinuses. Late stage disease has a poor prognosis, with 5 year survival less than 50%. The epidermal growth factor receptor (EGFR) is overexpressed in more than 90% of HNSCC, and the inhibition of EGFR is an established therapeutic strategy for HNSCC. However, sensitivity to EGFR-targeted therapy cannot be predicted from the expression level of EGFR. Only a subset of HNSCC patients benefit from anti-EGFR targeted therapy, suggesting that additional unknown pathways are involved in EGFR activation. We found that chloride channel accessory 2 (CLCA2) is frequently overexpressed in HNSCC and that its expression level predicts sensitivity to EGFR inhibitors in HNSCC cell lines. Knockdown of CLCA2 in HNSCC cancer cell line Fadu inhibited cell proliferation and sensitized cells to anoikis. Mechanistically, CLCA2 knockdown reduced EGFR signaling, which subsequently attenuated extracellular signal-regulated kinase (ERK). In addition, surface localization of cell-cell adhesion molecule E-cadherin was inhibited, corresponding to reduced cell aggregation. CLCA2 has recently been identified as a positive regulator of store operated calcium influx, and both EGFR activation and E-cadherin surface localization are known to depend on intracellular calcium release. We propose that CLCA2 overexpression in HNSCC allows the cell to better exploit EGFR proliferative signaling and protects from anoikis by promoting cell-cell aggregation. Thus, CLCA2 may serve both as a biomarker for sensitivity to EGFR inhibitors and as a target for inhibition itself. Citation Format: Yufang Yin, Randolph C. Elble. The role of CLCA2 in cell proliferation and survival of HNSCC—potential biomarker for sensitivity to EGFR inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5448.