TES is a novel focal adhesion protein with a role in cell spreading

Coutts, Amanda S.; MacKenzie, Elaine D.; Griffith, Elen; Black, Donald M.

doi:10.1242/jcs.00278

Cited by 92 publications

(138 citation statements)

References 44 publications

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“…6) in its 3 0 downstream region (À58 kb from the 3 0 -end). TES protein contains three conserved cysteine-rich zinc-binding motifs called LIM domains, suggesting that TES may play a role in protein-protein interaction and focal adhesion (Coutts et al, 2003). Methylation of the CpG island at the 5 0 end of TES is frequently occurred in ovarian cancer cells, and overexpression of TES in culture cells was shown to be growth-inhibitory (Tobias et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

et al. 2007

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The androgen receptor (AR) plays a key role as a transcriptional factor in prostate development and carcinogenesis. Identification of androgen-regulated genes is essential to elucidate the AR pathophysiology in prostate cancer. Here, we identified androgen target genes that are directly regulated by AR in LNCaP cells, by combining chromatin immunoprecipitation (ChIP) with tiling microarrays (ChIP-chip). ChIP-enriched or control DNAs from the cells treated with R1881 were hybridized with the ENCODE array, in which a set of regions representing approximately 1% of the whole genome. We chose 10 bona fide AR-binding sites (ARBSs) (Po1e-5) and validated their significant AR recruitment ligand dependently. Eight upregulated genes by R1881 were identified in the vicinity of the ARBSs. Among the upregulated genes, we focused on UGT1A and CDH2 as AR target genes, because the ARBSs close to these genes (in UGT1A distal promoter and CDH2 intron 1) were most significantly associated with acetylated histone H3/H4, RNA polymerase II and p160 family co-activators. Luciferase reporter constructs including those two ARBSs exhibited ligand-dependent transcriptional regulator/enhancer activities. The present study would be powerful to extend our knowledge of the diversity of androgen genetic network and steroid action in prostate cancer cells.

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Section: Discussionmentioning

confidence: 99%

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

et al. 2007

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“…Future studies will be needed to establish whether these ribosome genes function in the CeTOR pathway to regulate lifespan. Another interesting gene in this category is tag-224 (B0496.8), which encodes the C. elegans homolog of Testin, a cytoskeletal associated protein localized at focal adhesions and cell-cell contacts (Coutts et al, 2003). The gene encoding human Testin is a candidate tumor suppressor gene located at 7q31, a fragile chromosomal site (Tatarelli et al, 2000).…”

Section: Daf-16 Independent Genesmentioning

confidence: 99%

Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan

2007

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SummaryGenetic studies in many organisms suggest that an increased animal lifespan phenotype is often accompanied by enhanced resistance toward reactive oxygen species (ROS). In Caenorhabditis elegans , mutations in daf-2 , which encode an insulin/insulin-like growth factor 1 receptor-like molecule, lead to an extended animal lifespan and increased resistance to ROS. We have optimized an assay to monitor ROS resistance in worms using the ROS-generating chemical paraquat. We have employed this assay to screen the RNAi library along chromosomes III and IV for genes that, when silenced, confer paraquat resistance. The positive RNAi clones were subsequently screened for a lifespan extension phenotype. Using this approach, we have identified 84 genes that, when inactivated by RNAi, lead to significant increases in animal lifespan. Among the 84 genes, 29 were found to act in a manner dependent on daf-16 . DAF-16, a forkhead transcription factor, is known to integrate signals from multiple pathways, including the daf-2 pathway, to regulate animal lifespan. Most of the 84 genes have not been previously linked to aging, and potentially participate in important cellular processes such as signal transduction, cell-cell interaction, gene expression, protein degradation, and energy metabolism. Our screen has also identified a group of genes that potentially function in a nutrientsensing pathway to regulate lifespan in C. elegans . Our study provides a novel approach to identify genes involved in the regulation of aging.

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“…In particular, TES is a component of the focal adhesion complex, which is important in the regulation of epithelial physiology and localises to cell-matrix adhesions, cell-cell contacts and actin stress fibres. In mice, TES interacts and colocalises with a variety of cytoskeletal proteins, including zyxin, mena, VASP, talin and actin (36,37). Overexpression of TES decreased cell motility (36)(37)(38).…”

Section: Introductionmentioning

confidence: 99%

“…In mice, TES interacts and colocalises with a variety of cytoskeletal proteins, including zyxin, mena, VASP, talin and actin (36,37). Overexpression of TES decreased cell motility (36)(37)(38). Moreover, restoration of TES expression in breast cancer and uterine sarcoma cell lines inhibited their growth by induction of apoptosis (34).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of testin and survivin in breast cancer subtypes

et al. 2013

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Abstract. Testin (TES) is a putative tumour-suppressor gene downregulated in various types of cancers. Survivin is a nodal protein involved in multiple signalling pathways, tumour maintenance and inhibition of apoptosis. Previous studies indicate that TES and survivin can functionally interact and modulate cell death and proliferation in breast cancer cells. The aim of the present study was to investigate the expression and prognostic relevance of TES and survivin in breast cancer subtypes examining a large cohort of breast cancer patients. We determined the expression of TES and survivin by immunohistochemistry (IHC) in tissue samples from 242 breast cancer patients diagnosed between 1981 and 2009. The expression of these proteins was compared with clinical and pathological data. There was a significant association of nuclear survivin overexpression and TES downregulation with triple-negative tumours [P=0.009; univariate odds ratio (OR), 3.20; 95% CI, 1.34-7.66] (P=0.018; multivariate OR, 2.90; 95% CI, 1.20-6.97). A further significant correlation was observed between TES downregulation and the luminal B subtype (P=0.019, univariate OR: 2.90; 95% CI, 1.19-7.06) (P=0.032, multivariate OR, 2.67; 95% CI, 1.09-6.65), independent of survivin expression. Our results demonstrated a statistically significant association between TES downregulation and highly aggressive breast tumour subtypes, such as triplenegative and luminal B tumours, along with the prognostic relevance of nuclear expression of survivin. To our knowledge, this is the first demonstration of such an association.

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TES is a novel focal adhesion protein with a role in cell spreading

Cited by 92 publications

References 44 publications

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis

Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan

Differential expression of testin and survivin in breast cancer subtypes

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