Date of Graduation


Document Type

Thesis (MS)

Program Affiliation

Biomedical Sciences

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Don L. Gibbons

Committee Member

Hesham M. Amin

Committee Member

Lauren A. Byers

Committee Member

Faye M. Johnson

Committee Member

Jonathan M. Kurie


Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States due in part to the affinity of tumors to metastasize. Understanding the process which contributes to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-to-mesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT epithelial cells lose their cell adhesion properties and acquire a mesenchymal-like phenotype, allowing tumor cells to migrate from their epithelial cell community and invade remote locations. EMT is mediated by several signaling pathways, with transforming growth factor-beta (TGF-β) receiving attention for its up-regulation in the metastatic tumor microenvironment. TGF-β facilitates EMT through a variety of mechanisms but a prominent feature of TGF-β induced EMT is the activation of the transcription factor zinc finger E-box-binding homeobox 1 (Zeb1). Although Zeb1 has an established role in EMT the mechanism by which Zeb1 is regulated has not been fully elucidated. Here we demonstrate that Zeb1 undergoes post-translational modification and that this modification contributes to protein stability. We also expose novel Zeb1 interactions using the BioID method for proximity-dependent labeling of proteins. These results lead us to hypothesize that by targeting factors which mediate Zeb1 post-translational modification we may provide a therapeutic approach for metastasis suppression in NSCLC.


ZEB1, EMT, TGF-beta, post-translational modification



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