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The Role of NOTCH1 in Lung Cancer

Sinicropi-Yao, Sara Lu-Ming
http://orcid.org/0000-0003-2730-4939
http://rave.ohiolink.edu/etdc/view?acc_num=osu1522064811057979

Abstract Details

2018, Doctor of Philosophy, Ohio State University, Biomedical Sciences.
NOTCH1 is fundamentally involved in virtually every known cancer pathway, and dysregulation has been shown in multiple tumor types, where it can act as an oncogene or tumor suppressor depending on cellular context. Attempts to target NOTCH1 in solid tumors have been unsuccessful due to this complexity. A better understanding of NOTCH1 signaling is necessary before it can be leveraged as a therapeutic target. Using a novel approach, we examined correlations of gene expression with NOTCH1 in multiple solid tumors. Two-way hierarchical analysis of NOTCH1 co-expression patterns revealed that squamous cell carcinoma datasets clustered together, but apart from adenocarcinoma datasets. In lung adenocarcinoma, NOTCH1 co-expression was associated with genes that control angiogenesis and the immune system. Lung squamous carcinoma was associated with genes controlling cell cycle and mitosis. Results from immunohistochemistry and RNA sequencing studies supported the differential co- expression of NOTCH1 with angiogenesis, innate immunity, and mitotic processes. To bolster the co-expression data and better define how NOTCH1 was operating in the different lung cancer subtypes, shotgun proteomics was used to identify endogenous NOTCH1 interacting proteins. Interestingly, NOTCH1 interactions with mitochondrial proteins were prevalent in adenocarcinoma, but not squamous cell carcinoma. Our data help define novel mechanisms underlying the dual role of NOTCH1 in cancer and may lead to better therapeutic approaches.
David P. Carbone, MD, PhD (Advisor)
Kevin R. Coombes, PhD (Committee Chair)
John C. Byrd, MD (Committee Member)
Matthew D. Ringel, MD (Committee Member)
Stacey S. Huppert, PhD (Committee Member)
322 p.
Bioinformatics; Biology; Biomedical Research
Lung, Cancer, NOTCH1, Co-expression

Recommended Citations

Citations

  • Sinicropi-Yao, S. L.-M. (2018). The Role of NOTCH1 in Lung Cancer [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1522064811057979

    APA Style (7th edition)

  • Sinicropi-Yao, Sara. The Role of NOTCH1 in Lung Cancer. 2018. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1522064811057979.

    MLA Style (8th edition)

  • Sinicropi-Yao, Sara. "The Role of NOTCH1 in Lung Cancer." Doctoral dissertation, Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1522064811057979

    Chicago Manual of Style (17th edition)

osu1522064811057979
437
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This open access ETD is published by The Ohio State University and OhioLINK.