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Investigating the mechanisms of esophageal squamous cell carcinoma invasion (59.9)
Author(s) -
Lehman Heather,
Welsh Patricia,
Massé Julie,
Salzberg Ann,
Berg Arthur,
Stairs Douglas
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.59.9
Subject(s) - biology , cancer research , gene knockdown , epidermal growth factor receptor , oncogene , extracellular matrix , signal transduction , microarray analysis techniques , gene , cancer , gene expression , microbiology and biotechnology , cell cycle , genetics
Esophageal squamous cell carcinoma (ESCC) is a highly invasive disease and understanding the mechanisms involved is necessary to develop effective therapeutics to more successfully treat ESCC. p120‐catenin (p120ctn) is down‐regulated in 60% of ESCC tumors while the epidermal growth factor receptor (EGFR) is the most commonly overexpressed oncogene in ESCC. We hypothesized that p120ctn and EGFR both play integral roles in modulating ESCC invasion. Down‐regulation of p120ctn and overexpression of EGFR together in esophageal keratinocytes resulted in increased migration and invasion of these cells. Further, these cells invade into the extracellular matrix of our 3D organotypic culture system only when p120ctn and EGFR are manipulated. Ingenuity Pathway Analysis of gene expression microarray data generated from our 3D cultures identified cancer‐associated and metastatic genes as the most overrepresented in our datasets. We have identified a putative signaling pathway that involves PKD3 signaling through NFκB and PLAUR, resulting in increased MMP activity and invasion. We have identified increases in protein expression and activity of the components of this pathway. Knockdown of these genes will allow us to assess their role in ESCC invasion. In summary, we have identified a novel synergistic relationship between p120ctn and EGFR that involves a pathway including NFκB and PLAUR that induces ESCC invasion. Grant Funding Source : Supported by R00CA138498