Abstract
Abstract PURPOSE: In head and neck squamous cell carcinoma (HNSCC), mutations of p53 usually coexist with aberrant activation of NF-kappaB (NF-κB) and other transcription factors which promote tumor pathogenesis. However, how these factors mediate oncogenesis and metastasis is not fully understood. Herein we investigate the mechanisms by which p53 and NF-κB contribute to Epithelial-Mesenchymal Transition (EMT) in HNSCC. EXPERIMENTAL DESIGN: We evaluated the effects of p65 mutation on the molecular events of EMT in surgical specimens and HNSCC cell lines. We examined the correlation with tumor histologic features. RESULTS: In HNSCC cell lines with mutant p53, p65 knockdown promotes EMT. In contrast, in normal oral epithelial cells or HNSCC cells with WT p53, p65 over-expression, instead of knockdown, promotes EMT. Ablation of p53 in normal oral epithelial cells blocks p65 induced EMT. These findings are functionally corroborated herein in three-dimensional cell culture, anchorage-independent growth assays, and tumor cell migration assays. CONCLUSIONS: This is the first report indicating the role of p53 status in the NF-κB -induced promotion of EMT in HNSCC. Bortezomib-based regimens have been shown to have minimal activity in recurrent or metastatic head and neck cancer. Our new findings are important in understanding a possible basis for these clinical findings as well as defining important implications for targeted chemoprevention and therapy. Citation Format: Yuan Lin, Jie Luo, Elliot Abemayor, Sherven Sharma, Steven Dubinett, Maie St John. p53-dependent regulation of epithelial-to-mescenchymal transition by nf-κb 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 1141. doi:10.1158/1538-7445.AM2014-1141
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
