Repression of E-cadherin by SNAIL, ZEB1, and TWIST in invasive ductal carcinomas of the breast: a cooperative effort?

Montserrat, Núria; Gallardo, Alberto; Escuín, Daniel; Catasús, Lluis; Prat, Jaime; Gutiérrez-Avignó, Francisco José; Peiró, Gloria; Barnadas, Agustí; Lerma, Enrique

doi:10.1016/j.humpath.2010.05.019

Cited by 78 publications

(72 citation statements)

References 32 publications

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“…Although Snail1 is known to trigger EMT (18), a plasticity process providing tumor epithelial cells with invasive capacity, Snail1 expression and its consequences in carcinomas are controversial, with a few studies for breast cancer (28)(29)(30) and other cancers (31,32) reporting no significant association to patient survival. Here, we found that Snail1 expression in the tumor stroma, rather than in epithelial cells, associates with lymph node metastasis at diagnosis and has a robust prognostic value for early breast-infiltrating carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Snail1-Expressing Fibroblasts in the Tumor Microenvironment Display Mechanical Properties That Support Metastasis

et al. 2015

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Crosstalk between tumor and stromal cells in the tumor microenvironment alter its properties in ways that facilitate the invasive behavior of tumor cells. Here, we demonstrate that cancer-associated fibroblasts (CAF) increase the stiffness of the extracellular matrix (ECM) and promote anisotropic fiber orientation, two mechanical signals generated through a Snail1/RhoA/aSMAdependent mechanism that sustains oriented tumor cell migration and invasiveness. Snail1-depleted CAF failed to acquire myofibroblastic traits in response to TGFb, including RhoA activation, aSMA-positive stress fibers, increased fibronectin fibrillogenesis, and production of a stiff ECM with oriented fibers. Snail1 expression in human tumor-derived CAF was associated with an ability to organize the ECM. In coculture, a relatively smaller number of Snail1-expressing CAF were capable of imposing an anisotropic ECM architecture, compared with nonactivated fibroblasts. Pathologically, human breast cancers with Snail1 þ CAF tended to exhibit desmoplastic areas with anisotropic fibers, lymph node involvement, and poorer outcomes. Snail1 involvement in driving an ordered ECM was further confirmed in woundhealing experiments in mice, with Snail1 depletion preventing the anisotropic organization of granulation tissue and delaying wound healing. Overall, our results showed that inhibiting Snail1 function in CAF could prevent tumor-driven ECM reorganization and cancer invasion. Cancer Res; 75(2); 284-95. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

Snail1-Expressing Fibroblasts in the Tumor Microenvironment Display Mechanical Properties That Support Metastasis

et al. 2015

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“…Twist was not detected in this study; however, it may be involved. Twist reportedly may act through a different mechanism compared to Snail and Zeb proteins (25), and immunohistochemical analysis has detected a decreased expression of nuclear Twist in malignant pancreatic epithelium (26).…”

Section: Discussionmentioning

confidence: 99%

Nestin regulates epithelial-mesenchymal transition marker expression in pancreatic ductal adenocarcinoma cell lines

Hagio

Matsuda

Suzuki

et al. 2012

Molecular and Clinical Oncology

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Abstract. Nestin, a class VI intermediate filament, is a neuronal stem/progenitor cell marker that is also expressed by various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). We previously detected nestin expression in approximately 30% of PDAC cases, and found that nestin promotes the migration, invasion and metastasis of cells. Findings of recent studies have shown that epithelial mesenchymal transition (EMT) is important in the invasion and migration of cancer. In the present study, we investigated whether an altered nestin expression affected the expression levels of EMT markers in PDAC cells. Two human PDAC cell lines, PK-45H and KLM-1, in which nestin was suppressed and overexpressed, respectively, were used. The expression levels of the EMT-related molecules E-cadherin, Snail, Slug and Twist were analyzed using quantitative RT-PCR. Results showed that E-cadherin expression was decreased in nestin-overexpressed KLM-1 cells, and increased in nestin-suppressed PK-45H cells. Snail gene expression in the PDAC cells was altered concomitantly with the changes in nestin expression, while the Slug gene expression was significantly decreased in nestin-overexpressed KLM-1 cells. The Twist gene expression was below the detection limit in the two PDAC cell lines. The present findings indicated that nestin may be involved in the control of cancer behaviors in PDAC via the modulation of EMT-related molecules.

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“…ZEB1 has been investigated in prostate cancer, non-small-cell lung carcinoma, and invasive ductal breast cancer, but has not been investigated in HNSCC (Drake et al, 2010;Gemmill et al, 2011;Montserrat et al, 2011).…”

Section: Future Directionsmentioning

confidence: 99%

Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma

et al. 2012

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An understanding of the process by which tumor cells destroy the basement membrane of the surface epithelium, invade, and metastasize is essential to the development of novel treatment of head and neck squamous cell carcinoma (HNSCC). In recent years, there has been increased interest in the role of epithelial-mesenchymal transition (EMT) in invasion. EMT is a process that describes the development of motile, mesenchymal-like cells from non-motile parent epithelial cells. There are 3 known types of EMT that mediate development, wound healing, and carcinogenesis. This review summarizes studies of known EMT biomarkers in the context of HNSCC progression. The biomarkers discussed come from a wide range of proteins, including cell-surface proteins (E-cadherin, N-cadherin, and Integrins), cytoskeletal proteins (α-Smooth Muscle Actin, Vimentin, and β-catenin), extracellular matrix proteins (Collagens, Fibronectin, and Laminin), and transcription factors (SNAIL1, SNAIL2, TWIST, and LEF-1). Overall, the findings of these studies suggest that EMT mediates HNSCC progression. The mechanistic role of the EMT markers that have been associated with HNSCC should be more clearly defined if new anti-HNSCC therapies to block EMT progression are to be developed.KEY WORDS: disease progression, extracellular matrix, oral pathology, neoplasm invasiveness, biological markers, head and neck neoplasms.

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Repression of E-cadherin by SNAIL, ZEB1, and TWIST in invasive ductal carcinomas of the breast: a cooperative effort?

Cited by 78 publications

References 32 publications

Snail1-Expressing Fibroblasts in the Tumor Microenvironment Display Mechanical Properties That Support Metastasis

Snail1-Expressing Fibroblasts in the Tumor Microenvironment Display Mechanical Properties That Support Metastasis

Nestin regulates epithelial-mesenchymal transition marker expression in pancreatic ductal adenocarcinoma cell lines

Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma

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