title: Regulation of Multicellular Spheroids by MAPK and FYN Kinase.
abstract: Understanding of the biology of oral squamous cell carcinoma (SCC) has not progressed significantly in the past 60 years, with 5-year survival remaining at approximately 50%. The epidemic of Human Papilloma Virus and its associated SCC warrants a renewed emphasis on fully understanding this disease. We previously used the 3-dimensional multicellular spheroid (MCS) model system to evaluate SCC behavior more accurately. In this study, we determined that SCC growth in MCS approximates epithelial to mesenchymal transition. Organization of an MCS requires the full-length β6 integrin subunit and its maintenance requires mitogen-activated protein kinase (MAPK). Limiting FYN kinase activation results in the down-regulation of E-cadherin, β-catenin and an increase in expression of N-cadherin and SNAIL. These results indicate that the microenvironment and growth patterns in an MCS are complex and require MAPK and FYN kinase.
authors.affiliation: Department of Orofacial Sciences, University of California at San Francisco, San Francisco, CA, U.S.A.
authors.forename: Casey
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Orofacial Sciences, University of California at San Francisco, San Francisco, CA, U.S.A. Daniel.ramos@ucsf.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Ramos
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000472:pathogenicity; D051076:Proto-Oncogene Proteins c-fyn / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015820:Cadherins; D039641:Integrin beta Chains; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D051176:beta Catenin; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019950:Mitogen-Activated Protein Kinase 1
keywords: FYN Kinase; MAP kinase; Spheroid; multicellular spheroid formation