Date of Graduation
School of Medicine
Microbiology, Immunology, and Cell Biology
John Michael Ruppert.
Detachment of epithelial cells from matrix or attachment to an inappropriate matrix engages an apoptotic response known as anoikis, which prevents metastasis. Anoikis-resistance of tumor cells is critical for anchorage-independent growth and metastasis. Here we show two novel oncogenic pathways that confer resistance to anoikis in tumor cells. One pathway (chapter 2) signifies a new link between EMT and anoikis-resistance. In chapter 3, we present a new connection between inflammatory signaling pathways and anoikis-resistance. Cellular sensitivity to anoikis is compromised during the oncogenic epithelial-to-mesenchymal transition (EMT), through various mechanisms. Chapter 2 introduces a novel mechanism (NRAGE/TBX2/p14ARF) that is induced upon loss of E-cadherin and EMT, mediating anoikis resistance. The inflammatory-response transcription factor, NF-kB, contributes to anoikis-resistance and metastatic progression, through mechanisms that are understood incompletely. Deleted in Breast Cancer (DBC1) is over-expressed in several tumor types and correlates with a poorer prognosis in some cases. DBC1 suppressed anoikis in normal epithelial and breast cancer cell lines. Chapter 3 introduces a novel mechanism: DBC1 suppresses anoikis through enhancing canonical NF-kB signaling. This study will provide mechanisms for DBC1 to act as a tumor promoter, by providing a link between inflammation and anoikis-resistance and providing a potential target for anti-NF-eB/anti-cancer drugs.
Park, Sun Hee, "Regulation of anoikis by oncogenic pathways" (2013). Graduate Theses, Dissertations, and Problem Reports. 3658.