The origin of vimentin expression in invasive breast cancer: epithelial–mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential?

2005 ◽  
Vol 206 (4) ◽  
pp. 451-457 ◽  
Author(s):  
Eberhard Korsching ◽  
Jens Packeisen ◽  
Cornelia Liedtke ◽  
Daniela Hungermann ◽  
Pia Wülfing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progenitor Cells ◽  
Invasive Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Vimentin Expression ◽  
Differentiation Potential ◽  
Mesenchymal Transition

scholarly journals CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nataliia Petruk ◽  
Sanni Tuominen ◽  
Malin Åkerfelt ◽  
Jesse Mattsson ◽  
Jouko Sandholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Lung Metastases ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Cell Protrusion

AbstractCD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.

scholarly journals Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yifan Wang ◽  
Ruocen Liao ◽  
Xingyu Chen ◽  
Xuhua Ying ◽  
Guanping Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Abstract Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanisms of PAR1 in breast cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast cancer cells, and predicts poor prognosis in ER-negative and high-grade breast cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast cancer.

3D Models of Epithelial-Mesenchymal Transition in Breast Cancer Metastasis

2011 ◽  
Vol 16 (2) ◽  
pp. 141-154 ◽  
Author(s):  
Qun Li ◽  
Chaoyu Chen ◽  
Amit Kapadia ◽  
Qiong Zhou ◽  
Mary Kay Harper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Small Molecule ◽  
High Throughput Screening ◽  
Cancer Metastasis ◽  
Antitumor Agents ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Luciferase Reporter ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Despite advancements in therapies developed for the treatment of cancer, patient prognosis and mortality rates have improved minimally, and metastasis remains the primary cause of cancer mortality worldwide. An underlying mechanism promoting metastasis in many types of cancer is epithelial-mesenchymal transition (EMT). Here the authors report a novel 3D model of EMT and metastatic breast cancer suitable for high-throughput screening (HTS) drug discovery. The primary assay incorporates the expression of the prognostic biomarker vimentin, as a luciferase reporter of EMT, in basil-like/triple-negative MDA-MB-231 breast carcinoma spheroids. Using this model, the authors developed a number of known antitumor agents as control modulators of EMT. U0126, PKC412, PF2341066, dasatinib, and axitinib downregulated vimentin expression by 70% to 90% as compared to untreated spheroids. Counterassays were developed to measure spheroid viability and the invasive potential of MDA-MB-231 spheroids after small-molecule treatment and used to confirm hits from primary screening. Finally, the authors conducted a pilot screen to validate this model for HTS using a purified library of marine secondary metabolites. From 230 compounds screened, they obtained a Z′ score of 0.64, indicative of an excellent assay, and confirmed 4 hits, including isonaamidine B, papuamine, mycalolide E, and jaspamide. This HTS model demonstrates the potential to identify small-molecule modulators of EMT that could be used to discover novel antimetastatic agents for the treatment of cancer.

Significance of the vimentin expression in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1056-1056 ◽  
Author(s):  
Nami Yamashita ◽  
Eriko Tokunaga ◽  
Hiroyuki Kitao ◽  
Kimihiro Tanaka ◽  
Kenji Taketani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Cancer Cell Line ◽  
Japanese Patients ◽  
Vimentin Expression ◽  
Mesenchymal Transition

1056 Background: Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The treatment of patients with TNBC has been challenging due to the absence of these molecular targets and the heterogeneity of the disease. Therefore a better understanding of the molecular and histopathological features of TNBC and its heterogeniety is important for the development of a new therapeutic strategy and to improve the prognosis of TNBC. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin one of the most major factors associated with EMT was investigated in TNBC. Methods: Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14%) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative RT-PCR and immunohistochemistry. Results: The mRNA expression of vimentin was significantly upregulated in the basal type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p=0.0042) in TNBC compared to the other subtypes. Vimentin expression was associated with a younger age (p=0.016), high nuclear grade (p=0.023) and high Ki67 expression (p<0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p=0.0058) and overall survival (OS) (p=0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p=0.043). Vimentin expression was also associated with a significantly shorter RFS (p=0.021) and OS (p=0.017) in patients with basal-like breast cancer (BLBC). Conclusions: The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.

Epithelial mesenchymal transition in early invasive breast cancer: an immunohistochemical and reverse phase protein array study

2014 ◽  
Vol 145 (2) ◽  
pp. 339-348 ◽  
Author(s):  
Mohammed A. Aleskandarany ◽  
Ola H. Negm ◽  
Andrew R. Green ◽  
Mohamed A. H. Ahmed ◽  
Christopher C. Nolan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Protein Array ◽  
Reverse Phase Protein Array ◽  
Reverse Phase ◽  
Mesenchymal Transition ◽  
Phase Protein

scholarly journals O-55 Translational landscape of Epithelial Mesenchymal Transition in molecular classes of invasive breast cancer

2010 ◽  
Vol 8 (6) ◽  
pp. 21
Author(s):  
Mohammed A. Aleskandarany ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
Des G. Powe ◽  
Ian O. Ellis
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition
Sign in / Sign up

Export Citation Format

Share Document