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J. Amann

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-019 - Dual Role of Notch in Lung Cancer (ID 7578)

      09:30 - 16:00  |  Author(s): J. Amann

      • Abstract

      Anomalies in the family of Notch receptors (1, 2, 3, and 4) have been implicated in a range of solid tumors, including lung cancer. There is growing evidence that Notch plays an oncogenic and tumor suppressor role in adenocarcinoma and lung squamous cell carcinoma, respectively. Gaining a complete understanding of the mechanisms underlying these opposing activities in lung cancer is key to the development of novel targeted therapy approaches.

      The Cancer Genome Atlas (TCGA) datasets were used to look at gene co-expression patterns of Notch in lung adenocarcinoma and lung squamous cell carcinoma. Biological pathways implicated by gene families were assessed using functional annotation tools (DAVID, ToppGene, and IPA). In vitro and in vivo knockdown studies assessed the functional role of Notch in lung cancer.

      Co-expression analysis supports the hypothesis that Notch is co-expressed with different genes in lung adenocarcinoma and squamous cell carcinoma. Knockdown of Notch in vitro and in vivo support our in silico finding of opposing effects of Notch. Our analysis implicates genes associated with metabolic pathways, angiogenesis and cell cycle that may underlie the differential role of Notch in lung adenocarcinoma and squamous cell carcinoma.

      These results support the hypothesis differences in the Notch co-expression may underlie its opposing roles in lung adenocarcinoma and squamous cell carcinoma. These finding help unravel the context dependent role of Notch as an oncogene and tumor suppressor in subtypes of lung cancer. Understanding the similarities and differences in co-expression patterns can improve our understanding of the regulatory mechanisms of Notch and strategies for its clinical development as single agent or in combination.