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IDENTIFICATION OF EPITHELIAL STROMAL INTERACTION 1 AND EPIDERMAL GROWTH FACTOR RECEPTOR AS NOVEL KR(&)#220;PPEL-LIKE FACTOR 8 TARGETS IN PROMOTING BREAST CANCER PROGRESSION

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Date Issued:
2013
Abstract/Description:
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 Kr(&)#252;ppel-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-?B through binding valosin containing protein (VCP) and subsequent degradation of I?B?, whereas EGFR promotes tumor growth and metastasis via activation of ERK. Taken together, these data identify EPSTI1 and EGFR as novel KLF8 targets in breast cancer and suggest that KLF8 may be targeted for new effective treatment of breast cancer.
Title: IDENTIFICATION OF EPITHELIAL STROMAL INTERACTION 1 AND EPIDERMAL GROWTH FACTOR RECEPTOR AS NOVEL KR(&)#220;PPEL-LIKE FACTOR 8 TARGETS IN PROMOTING BREAST CANCER PROGRESSION.
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Name(s): Li, Tianshu, Author
Zhao, Jihe, Committee Chair
Khaled, Annette, Committee Member
Altomare, Deborah, Committee Member
Lambert, Stephen, Committee Member
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2013
Publisher: University of Central Florida
Language(s): English
Abstract/Description: 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 Kr(&)#252;ppel-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-?B through binding valosin containing protein (VCP) and subsequent degradation of I?B?, whereas EGFR promotes tumor growth and metastasis via activation of ERK. Taken together, these data identify EPSTI1 and EGFR as novel KLF8 targets in breast cancer and suggest that KLF8 may be targeted for new effective treatment of breast cancer.
Identifier: CFE0005366 (IID), ucf:50474 (fedora)
Note(s): 2013-12-01
Ph.D.
Medicine, Molecular Biology and Microbiology
Doctoral
This record was generated from author submitted information.
Subject(s): KLF8 -- EPSTI1 -- EGFR -- breast cancer -- invasion -- metastasis
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFE0005366
Restrictions on Access: public 2014-06-15
Host Institution: UCF

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