Keywords

Klf8, epsti1, egfr, breast cancer, invasion, metastasis

Abstract

Breast cancer is the major cause of cancer death among women worldwide. Understanding the mechanisms underlying breast cancer progression remains urgent for developing effective treatment strategies to eliminate breast cancer mortality. Our recent studies have demonstrated that Krüppel-like transcriptional factor 8 (KLF8) plays a critical role for breast cancer progression. Other studies have shown that Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells and epidermal growth factor receptor (EGFR) are highly overexpressed in aggressively invasive breast carcinomas including triple negative breast cancers. In this thesis project, we demonstrate high co-overexpression of KLF8 with EPSTI1 as well as EGFR in invasive breast cancer cells and patient tumors. We also show that KLF8 upregulates the expression of EPSTI1 by directly binding and activating the EPSTI1 gene promoter, and KLF8 upregulates the expression of EGFR not only by directly activating the EGFR gene promoter but also by preventing EGFR translation from microRNA141-dependent inhibition. Genetic, signaling and animal cancer model analyses indicate that downstream of KLF8, EPSTI1 promotes the tumor invasion and metastasis by activating NF-κB through binding valosin containing protein (VCP) and subsequent degradation of IκBα, whereas EGFR promotes tumor growth and metastasis via activation of ERK. Taken together, these data identify EPSTI1 and EGFR as novel iv KLF8 targets in breast cancer and suggest that KLF8 may be targeted for new effective treatment of breast cancer

Notes

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Graduation Date

2013

Semester

Fall

Advisor

Zhao, Jihe

Degree

Doctor of Philosophy (Ph.D.)

College

College of Medicine

Department

Molecular Biology and Microbiology

Degree Program

Biomedical Sciences

Format

application/pdf

Identifier

CFE0005366

URL

http://purl.fcla.edu/fcla/etd/CFE0005366

Language

English

Release Date

June 2014

Length of Campus-only Access

None

Access Status

Doctoral Dissertation (Open Access)

Subjects

Dissertations, Academic -- Medicine, Medicine -- Dissertations, Academic

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