The role of TLE1 in synovial sarcoma

Seo, Sung Wook; Lee, Hyewon; Lee, Hyun Il; Kim, Han‐Soo

doi:10.1002/jor.21318

Cited by 28 publications

(22 citation statements)

References 27 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 The inhibition of TLE1 affects not only cell proliferation but also the apoptosis pathway by suppressing Bcl-2 expression. 1 Although there is a good correlation between TLE1 expression and SS18 break-apart, their biological roles and relationship remain largely unknown. TLE1 gene is located at chromosome 9q21.32, whereas SS18 gene is at 18q11.2.…”

Section: Resultsmentioning

confidence: 99%

“…1,2 In several DNA microarray studies, TLE1 gene was found consistently overexpressed in synovial sarcomas. [3][4][5] By Immunohistochemistry (IHC) in formalin-fixed, paraffinembedded tissues, TLE1 expression was identified in more than 95% of synovial sarcomas, with weak or no expression in nonsynovial sarcomas, and therefore it was considered a robust diagnostic immunohistochemical marker for synovial sarcoma.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Specificity of TLE1 Expression in Unclassified High-grade Sarcomas for the Diagnosis of Synovial Sarcoma

Valente

Tull

Zhang

2013

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

Expression of the transducin-like enhancer of split 1 (TLE1) by immunohistochemistry (IHC) has been widely used as a biomarker for the diagnosis of synovial sarcoma. Although TLE1 expression can be identified in more than 90% of synovial sarcomas, positive staining has been reported in up to one third of nonsynovial sarcomas, including peripheral nerve sheath tumors and neoplasms of fibrous and adipose tissues. The low specificity of this test in soft tissue tumors raises concern on its clinical application as a diagnostic biomarker. As synovial sarcoma is frequent among the differential diagnosis of unclassified high-grade sarcomas, and considering that the specificity of TLE1 antibody in this tumor group remains unclear, we evaluated TLE1 expression by IHC in 42 unclassified high-grade sarcomas. SS18 (SYT) gene break-apart analyses by fluorescence in situ hybridization were simultaneously performed as a gold standard biomarker for synovial sarcoma. Five cases that were positive for the SS18 break-apart by fluorescence in situ hybridization were also positive for TLE1 by IHC, whereas the remaining 37 cases negative for SS18 break-apart were all negative for TLE1. The results showed no evidence of nonspecific TLE1 expression in the nonsynovial high-grade sarcomas. We concluded that TLE1 is a highly specific biomarker for synovial sarcoma in the setting of differential diagnosis of unclassified high-grade sarcomas.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Specificity of TLE1 Expression in Unclassified High-grade Sarcomas for the Diagnosis of Synovial Sarcoma

Valente

Tull

Zhang

2013

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

show abstract

“…Experimental knockdown of TLE1 in fibroblasts and synovial cells did not affect cell proliferation or enhance the cytotoxicity of chemotherapy, which suggests that TLE1 can be a good target for selectively treating synovial sarcoma without causing damage to the host tissue. However, further studies will be needed to determine a potential therapeutic role for TLE1 [32]. In the largest series of 259 cases of molecularly confirmed synovial sarcomas using a TMA, TLE1 was reported positive in 96%, but negative in others [18-20, 24, 25].…”

Section: Discussionmentioning

confidence: 99%

TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas

et al. 2011

View full text Add to dashboard Cite

Pleuropulmonary synovial sarcoma (PPSS) is a rare entity, similar to synovial sarcoma of soft tissue (STSS). There are 120 published cases of PPSS, but no studies have explored the expression of TLE1. In soft tissues, it has been proven a useful marker, but in tumors of other sites, its expression has not been explored. The main objective was to study the expression and diagnostic sensitivity and specificity of TLE1 in a group of PPSS, of which the diagnosis was corroborated by fluorescence in situ hybridization confirming t(X;18) in a tissue microarray. Immunohistochemistry including TLE1, vimentin, CD99, CD56, bcl-2, AE1-AE3, EMA, CD34, CK7, CK19, calponin, and S-100 was performed on all PPSS and on 25 control cases (five carcinomas, ten mesotheliomas, and ten thoracic sarcomas). TLE1 was positive in 11 cases (73.3%); bcl-2 and vimentin in 100%; calponin and CD56 in 26.6%; CD99, CK AE1-AE3, CK19, CK7, and EMA in 80%; and S100 negative in all. The only biphasic PPSS was positive for epithelial markers only in the epithelial component. TLE1 was negative in all control cases. TLE1 is expressed in 73% of PPSS, a value inferior to that reported in STSS, but is highly specific for PPSS. TLE1 may therefore be of value in the differential diagnosis of PPSS, but should be used in a panel of antibodies.

show abstract

“…Exogenous TLE1 expression stimulated anchorage-independent growth in chicken embryo fibroblast (9). As a negative regulator of apoptosis, TLE1 inhibited low potassium-induced apoptosis in neurons (10) and protected synovial sarcoma cells from doxorubicin-mediated apoptosis (11). In line with its anti-apoptotic function, we have found that TLE1 specifically inhibited the caspase-independent cell death induced by Bit1 (Bcl2-inhibitor of transcription 1) in several types of malignant cells (12).…”

Section: Introductionmentioning

confidence: 99%

TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin

Yao

Ireland

Pham

et al. 2014

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The Groucho transcriptional corepressor TLE1 protein has recently been shown to be a putative lung specific oncogene, but its underlying oncogenic activity in lung cancer has not been fully elucidated. In this report, we investigated whether TLE1 regulates lung cancer aggressiveness using the human lung adenocarcinoma cell line A549 as a model system. Through a combination of genetic approaches, we found that TLE1 potentiates Epithelial-to-Mesenchymal Transition (EMT) in A549 cells in part through suppression of the tumor suppressor gene E-cadherin. Exogenous expression of TLE1 in A549 cells resulted in heightened EMT phenotypes (enhanced fibroblastoid morphology and increased cell migratory potential) and in molecular alterations characteristic of EMT (downregulation of the epithelial marker E-cadherin and upregulation of the mesenchymal marker Vimentin). Conversely, downregulation of endogenous TLE1 expression in these cells resulted in reversal of basal EMT characterized by a cuboidal-like epithelial cell phenotype, reduced cell motility, and upregulated E-cadherin expression. Mechanistic studies showed that TLE1 suppresses E-cadherin expression at the transcriptional level in part by recruiting Histone Deacetylase (HDAC) activity to the E-cadherin promoter. Consistently, the HDAC inhibitor TSA partially reversed the TLE1-induced E-cadherin downregulation and cell migration, suggesting a role for HDACs in TLE1-mediated transcriptional repression of E-cadherin and EMT function. These findings uncover a novel role of TLE1 in regulating EMT in A549 cells through its repressive effect on E-cadherin and provide a mechanism for TLE1 oncogenic activity in lung cancer.

show abstract

The role of TLE1 in synovial sarcoma

Cited by 28 publications

References 27 publications

Specificity of TLE1 Expression in Unclassified High-grade Sarcomas for the Diagnosis of Synovial Sarcoma

Specificity of TLE1 Expression in Unclassified High-grade Sarcomas for the Diagnosis of Synovial Sarcoma

TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas

TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin

Contact Info

Product

Resources

About