Abstract 2882: Coronin 1B overexpression promotes invasion of HPV- HNSCC

Introduction: Amplification of chromosome 11q13 is the most common DNA aberration in human papilloma virus negative (HPV-) head and neck squamous cell carcinoma. (HSNCC). The 11q13 region encodes various genes known to enhance invasion and drive tumor progression. CORO1B (coronin 1B) flanks the core 11q13 region and is amplified in 7-14% of HNSCC cases. Coronin 1B governs cell motility in fibroblasts by negatively regulating the ability of the Arp 2/3 nucleator cortactin to stabilize the actin cytoskeleton during mesenchymal cell migration. This study seeks to determine the impact of CORO1B amplification and protein overexpression in driving HNSCC progression. Experimental Procedures: Two patient cohorts were used to assess the impact of CORO1B amplification or overexpression on patient outcome. In addition, HNSCC cell lines lacking or overexpressing coronin 1B were assayed for invadopodia function using gelatin degradation assays. Three-dimensional invasion was analyzed using tumor spheroid and organotypic assays. Invasive and cervical lymph node metastatic potential of CORO1B was evaluated using knockdown and overexpression cells in orthotopic tongue models. Data Summary: CORO1B amplification and overexpression in patient tumors correlates with enhanced patient decline. Coronin 1B-null cell lines display decreased invadopodia function, with a 30-60% decrease in extracellular matrix-mimicking gelatin degradation. HNSCC tumor spheroids lacking coronin 1B expression decreased 3D invasion in native collagen I, while overexpression enhanced invasive capabilities in both tumor spheroids and organotypic cultures. Coronin 1B knockdown cells show decreased lymph node metastasis, while mice with tumors overexpression coronin 1B have enhanced lymph node metastasis and decreased survival. CORO1B amplification protein overexpression predict poor overall patient survival. Conclusion: The identification of coronin 1B overexpression as an important mediator in promoting HNSCC invasive processes may define a novel aggressive subset of locoregional involved HNSCC, warranting enhanced clinical intervention. Citation Format: Jessica L. Allen, Elyse L. Walk, Kristen L. Rhodes, Steven M. Markwell, Brenen W. Papenberg, Hong Wu, Marileila Garcia, James E. Bear, Scott A. Weed. Coronin 1B overexpression promotes invasion of HPV- HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2882.