Regulation of vimentin by SIP1 in human epithelial breast tumor cells

Bindels, S; Mestdagt, Mélanie; Vandewalle, Cindy; Jacobs, Nathalie; Volders, Laure; Noël, Agnès; Roy, Frans van; Berx, Geert; Foidart, Jean‐Michel; Gilles, Christine

doi:10.1038/sj.onc.1209511

Cited by 161 publications

(146 citation statements)

References 58 publications

(59 reference statements)

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“…A panel of genes that drive EMT (vimentin, SIP1, Snail1, Twist1, MMP2, and MMP9) was unanimously inhibited in HCC1806-ShNCT cells, and up-regulated in MCF10ANCT cells. Regulation of vimentin was the most pronounced in both contexts and was coupled to a marked modulation of its transcriptional regulator SIP1 (40). Simultaneous inhibition of all four Notch receptors by siRNA in other cell lines was capable of reducing vimentin protein levels (41).…”

Section: Discussionmentioning

confidence: 93%

Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo

Lombardo

Filipović

Molyneux

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Nicastrin (NCT) is a crucial component of the γ-secretase (GS) enzyme, which prompted investigations into its biological role in cancer. We have previously shown that nicastrin is overexpressed in breast cancer (BC), conferring worse overall survival in invasive, ERα negative patients. Here, we used 2D and 3D Matrigel, anchorage-independent growth conditions and a breast cancer xenograft mouse model to assess the impact of nicastrin on breast cancer stem cell (BCSC) propagation and invasion in vitro and tumor growth in vivo. Stable knockdown of nicastrin in HCC1806 breast cancer cells reduced cell invasion by 51.4 ± 1.7%, accompanied by a morphological change to a rounded cell phenotype and downregulation of vimentin, Snail, Twist, MMP2, and MMP9. We observed a reduction of the pool of CD44 + /CD24 − and ALDH1 high breast cancer stem cells by threefold and twofold, respectively, and a reduction by 2.6-fold of the mammospheres formation. Nicastrin overexpression in nontransformed MCF10A cells caused an induction of epithelial to mesenchymal regulators, as well as a fivefold increased ALDH1 activity, a threefold enrichment for CD44 + /CD24 − stem cells, and a 3.2-fold enhanced mammosphere-forming capacity. Using the γ-sescretase inhibiton, Notch1/4 siRNA, and Akt inhibition, we show that nicastrin regulates breast cancer stem cells partly through Notch1 and the Akt pathway. Exploiting serial dilution transplantation of the HCC1806 cells expressing nicastrin and HCC1806 stably depleted of nicastrin, in vivo, we demonstrate that nicastrin inhibition may be relevant for the reduced tumorigenicity of breast cancer cells. These data could serve as a benchmark for development of nicastrin-targeted therapies in breast cancer. metastasis | mammary tumor

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Section: Discussionmentioning

confidence: 93%

Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo

Lombardo

Filipović

Molyneux

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…29 In contrast, the mouse Met-1 AS-OPN EMT tumors, with increased expression of Snail and it's downstream pathway (Supplementary Table 2), were associated with decreased metastases. 18 Further, the spindle-cell tumors from our other cohorts were not associated with documented metastases.…”

Section: Discussionmentioning

confidence: 99%

EMT tumorigenesis in the mouse mammary gland

Damonte

Gregg

Borowsky

et al. 2007

Laboratory Investigation

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The term EMT (epithelial-mesenchymal transition) is used in many settings. This term is used to describe the mechanisms facilitating cellular repositioning and redeployment during embryonic development and tissue reconstruction after injury. Recently, EMT has also been applied to potential mechanisms for malignant progression and has appeared as a specific diagnostic category of tumors. In mice, most 'EMT' tumors have a spindle cell phenotype. The definition of EMT is controversial because spindle cell tumors are not common in humans, especially in human breast cancers. Spindle cell tumors of the mouse mammary gland have been observed for many years where they are usually classified as sarcomas or carcinosarcomas. Genetically engineered mice develop mammary spindle cell tumors that appear to arise in the epithelium and undergo EMT. To better understand the origin and evolution of these spindle cell tumors in progression and metastases, seven cohorts of spindle cell tumors from the archives of the University of California, Davis Mutant Mouse Pathology Laboratory were studied. This study provides experimental and immunohistochemical evidence of EMT showing that dual epithelial and mesenchymal staining of tumor spindle cells identifies some, but not all, EMT-type tumors in the mouse. This suggests that potential EMT tumors are best designated EMT-phenotype tumors.

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“…Its expression is higher in migratory epithelial cells and may contribute to the migratory and invasive phenotype of metastatic cells (Bindels et al, 2006). Significant correlations between high vimentin tumour cell expression and poor prognosis have previously been reported both in hepatocellular (Hu et al, 2004) and breast carcinoma (Dandachi et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

The prognostic impact of NF-κB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer

et al. 2008

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Vimentin, nuclear factor-kB (NF-kB) p105, fascin, E-cadherin, TGF-b, Par6 and atypical PKC are molecular markers that play an important role in cell differentiation. Herein, we investigate their prognostic impact in primary non-small-cell carcinoma (NSCLC). Tumour tissue samples from 335 resected patients with stage I -IIIA were used. Tissue microarrays were constructed from duplicate cores of both neoplastic cells and stromal cells and were immunohistochemically evaluated. In univariate analyses, high tumour epithelial cell expressions of NF-kB p105 (P ¼ 0.02) and E-cadherin (P ¼ 0.03) were positive prognostic indicators for disease-specific survival (DSS), whereas high tumour epithelial cell expression of vimentin (P ¼ 0.001) was a negative prognostic indicator. High expression of NF-kB p105 (P ¼ 0.001) and Par6 (P ¼ 0.0001) in the stromal compartment correlated with a good prognosis. In multivariate analyses, the tumour epithelial cell expression of NF-kB p105 (P ¼ 0.0001) and vimentin (P ¼ 0.005) and the stromal cell expression of NF-kB p105 (P ¼ 0.007) and Par6 (P ¼ 0.0001) were independent prognostic factors for DSS. High expression of NF-kB p105 and low expression of vimentin in tumour epithelial cells are independent predictors of better survival in primary NSCLC. In stromal cells, high expressions of NF-kB p105 and Par6 are both favourable independent prognostic indicators.

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Regulation of vimentin by SIP1 in human epithelial breast tumor cells

Cited by 161 publications

References 58 publications

Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo

Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo

EMT tumorigenesis in the mouse mammary gland

The prognostic impact of NF-κB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer

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