ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer.

Published on Aug 30, 2018in Molecules3.267
· DOI :10.3390/MOLECULES23092191
Ian Y. Luk2
Estimated H-index: 2
,
Camilla M. Reehorst2
Estimated H-index: 2
,
John M. Mariadason57
Estimated H-index: 57
Sources
Abstract
The epithelium-specific ETS (ESE) transcription factors (ELF3, ELF5, EHF and SPDEF) are defined by their highly conserved ETS DNA binding domain and predominant epithelial-specific expression profile. ESE transcription factors maintain normal cell homeostasis and differentiation of a number of epithelial tissues, and their genetic alteration and deregulated expression has been linked to the progression of several epithelial cancers. Herein we review the normal function of the ESE transcription factors, the mechanisms by which they are dysregulated in cancers, and the current evidence for their role in cancer progression. Finally, we discuss potential therapeutic strategies for targeting or reactivating these factors as a novel means of cancer treatment.
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#1Yuan Chin Tsai (TMU: Taipei Medical University)H-Index: 4
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Abstract ELF3 is one of the member of transcription factors from E-twenty-six family, its role varies in different types of cancer. However, the role and specific mechanisms of ELF3 in the development of non-small cell lung cancer (NSCLC) still remains largely unknown. In our study, ELF3 was observed to be upregulated in NSCLC tissues compared to the corresponding normal lung tissue at mRNA and protein levels, and its expression level was correlated with the overall survival of patients with NSC...
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The ETS transcription factor ESE-1/Elf3 is overexpressed in breast cancer, controls transformation properties in mammary epithelial cells, and is most clinically relevant in HER2+ breast cancer. Here we show that ESE-1 knockdown, via shRNA, inhibits proliferation, clonogenicity, and anchorage-independent growth in HER2+, trastuzumab-resistant breast cancer cell lines HR20 (derived from HER2+ ER+ BT474) and Pool2 (derived from HER2+ ER- SKBR3 cells). ESE-1 knockdown in HR20 cells inhibited HER2/p...
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Colorectal cancers (CRCs) are characterized by global hypomethylation and promoter-specific DNA methylation. A subset of CRCs with extensive and co-ordinate patterns of promoter methylation has also been identified, termed the CpG-island methylator phenotype. Some genes methylated in CRC are established tumor suppressors; however, for the majority, direct roles in disease initiation or progression have not been established. Herein, we examine functional evidence of specific methylated genes cont...
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Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen–binding protein transforming growth factor–β (TGFβ)–induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR...
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Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) family of transcription factors. To investigate its role in development and epithelial homeostasis, we generated a series of novel mouse strains in which the Ets DNA-binding domain of Ehf was deleted in all tissues (Ehf-/-) or specifically in the gut epithelium. Ehf-/- mice were born at the expected Mendelian ratio, but showed reduced body weight gain, and developed a series of pathologies requiring most Ehf-/- mice to ...
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