Expression of Snail protein in tumor–stroma interface

Francı́, Clara; Takkunen, Minna; Dave, Natàlia; Alameda, Francesc; Gomez, Shawn M.; Rodríguez, Rafael Gómez; Escrivà, Maria; Montserrat-Sentís, Bàrbara; Baró, Teresa; Garrido, Marta; Bonilla, Félix; Virtanen, Ismo; Herreros, Antonio Garcı́a de

doi:10.1038/sj.onc.1209519

Cited by 196 publications

(237 citation statements)

References 44 publications

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“…We found coexpression of E-cadherin and Snail in 36.1% of primary tumours and in 53.8% of metastases. These results are in accordance with previous studies on endometrial and colon cancer (Franci et al, 2006;Blechschmidt et al, 2007), although it is not yet understood why Snail expression does not lead to E-cadherin downregulation in these cases.…”

Section: Discussionsupporting

confidence: 92%

“…In addition to Snail-positive carcinoma cells, we also found tumour-associated stromal cells showing a positive immunoreactivity for Snail. Snail-positive stromal cells have been described previously by us and by Franci et al (2006) in endometrial and colon cancer, respectively. This raises the question whether these Snailpositive stromal cells represent former tumour cells that have undergone mesenchymal transition.…”

Section: Discussionsupporting

confidence: 58%

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The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

et al. 2007

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Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (Po0.001). This correlation was found for Snail expression as well (Po0.001). There was a significant (P ¼ 0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P ¼ 0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P ¼ 0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 58%

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

et al. 2007

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“…25 The antibody details are provided in Supplementary Table 6. 26 Immunofluorescence preparations were examined using an Eclipse 90i microscope system (Nikon) and processed with Image-J analysis software.…”

Section: Western Blotting and Immunofluorescencementioning

confidence: 99%

A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

et al. 2015

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Although TAZ, the final effector of the Hippo pathway that modulates epithelial to mesenchymal transition and stemness, has been implicated in the development of different types of cancer, its role in endometrial cancer has not yet been studied. Thus, we evaluated the expression of TAZ in different types of endometrial cancer by immunohistochemistry. TAZ expression was detected in 76% of undifferentiated endometrial carcinomas, 54% of endometrial carcinosarcomas, 46% of endometrial serous carcinomas, 36% of grade 3 endometrioid carcinomas, and 18% of grade 1-2 endometrioid carcinomas, with statistically significant differences. We analyzed the WWTR1 gene that encodes TAZ by FISH and MassARRAY spectrometry, ruling out gene amplification and differential promoter methylation as the main mechanisms that modulate TAZ expression in endometrial tumors. However, we did detect a significant association between Scribble hypoexpression and delocalization with TAZ expression. Moreover, we demonstrated that TAZ promoted invasiveness, and it favored cell motility and tumor growth, in endometrial cancer cell lines. In addition, TAZ expression was associated with the transition from an epithelial to mesenchymal phenotype, both in vitro and in human tumors. Together, these data reveal a previously unknown role for TAZ and the Hippo pathway in the progression of aggressive subtypes of endometrial cancer. Modern Pathology (2015Pathology ( ) 28, 1492Pathology ( -1503 doi:10.1038/modpathol.2015 published online 18 September 2015 In developed countries, endometrial carcinoma is the most common malignant tumor of the female genital tract. 1 On the basis of epidemiological, clinical, pathological, and molecular features, endometrial carcinoma can be classified into at least two main categories: 2 type I estrogen-dependent carcinomas that account for 80-85% of cases and that are typically represented by low-grade (grade 1 and 2) endometrioid carcinomas, and type II endometrial carcinomas that are not estrogen dependent and that are mainly represented by a serous subtype but also by other high-grade histological tumors like clear cell or undifferentiated carcinomas. 2 In endometrial carcinoma, the epithelial to mesenchymal transition has been associated with high-grade and aggressive features. [3][4][5][6] Epithelial to

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“…The slides were cooled and treated with peroxidase-blocking solution (Dako) for 5 min. Sections were then immunostained with SNAIL (EC3 clone) (Franci et al, 2006) hybridoma supernatant by the two-stage peroxidasebased EnVision technique (Dako), counterstained with hematoxylin, and mounted. Incubations, either omitting the specific antibody or containing unrelated antibodies, were used as a control of the technique.…”

Section: Proteomic Assaysmentioning

confidence: 99%

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

et al. 2009

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SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P ¼ 0.047 and P ¼ 0.014, respectively) and NAT lacking SNAI1 expression (P ¼ 0.054 and P ¼ 0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r ¼ 0.39; P ¼ 0.027) and inversely to CDH1 in NAT (r ¼ À0.46; P ¼ 0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

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Expression of Snail protein in tumor–stroma interface

Cited by 196 publications

References 44 publications

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

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