scholarly journals Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening

Stem Cells ◽  
2017 ◽  
Vol 35 (8) ◽  
pp. 1898-1912 ◽  
Author(s):  
Anne G. Christensen ◽  
Sidse Ehmsen ◽  
Mikkel G. Terp ◽  
Richa Batra ◽  
Nicolas Alcaraz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Drug Screening ◽  
Triple Negative ◽  
Cell Model ◽  
Model System ◽  
Tumor Initiating Cells ◽  
Cell Model System

scholarly journals TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiahui Xu ◽  
Xiaoli Yang ◽  
Qiaodan Deng ◽  
Cong Yang ◽  
Dong Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Vasculogenic Mimicry ◽  
Regulatory Mechanisms ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Tumor Endothelial Marker 8

AbstractEnhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ERα trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.

New docetaxel-peptide conjugate for the treatment of sortilin-positive triple-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12556-e12556
Author(s):  
Michel Demeule ◽  
Borhane Annabi ◽  
Jean-Christophe Currie ◽  
Alain Larocque ◽  
Cyndia Charfi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Regression ◽  
Cell Model ◽  
Molecular Signature ◽  
Specific Gene ◽  
Real Time System

e12556 Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease which still lacks defined molecular biomarkers. In the last decade, targeting of specific gene/protein molecular signature of tumors emerged among the best anticancer strategies. Recently, increased expression of the Sortilin (SORT1) receptor has been reported in TNBC patients. Given SORT1 functions in protein internalization, sorting and trafficking, we developed a new peptide-anticancer drug conjugation platform to target SORT1-positive breast cancer by linking Docetaxel to a peptide (KA-peptide) that specifically targets SORT1. Methods: MDA-MB-231 cells were used as a TNBC cell model for in vitro and in vivo xenograft (CD1 nude mice) assays. Cell migration was assessed using the xCELLigence real-time system, whereas MTT assay was used for cell proliferation analysis. Apoptosis biomarkers expression was assessed by immunoblotting. Results: In MDA-MB-231, the Docetaxel-KA-peptide conjugate (DoceKA) exerted potent anti-proliferative and anti-migratory activities in vitro. DoceKA triggered faster and higher cell death mechanisms than did free Docetaxel alone. The apoptotic and anti-migratory effects were reversed by the SORT1 ligands Neurotensin and Progranulin, and upon siRNA-mediated silencing of SORT1. DoceKA altered microtubules polymerization and triggered the down-regulation of IL-6, Survivin, Bcl-xL and mutant p53 pro-survival biomarkers. In vivo, DoceKA exhibited a greater tumor regression capacity with a prolonged survival in a murine MDA-MB-231 xenograft tumor model than did Docetaxel. Conclusions: Collectively, we demonstrate that DoceKA is specifically internalized through a receptor-mediated mechanism. Such property allows for targeting SORT1-positive breast cancers, and makes DoceKA a promising novel therapy for the treatment of TNBC.

scholarly journals Tumor-Initiating Cells and FZD8 Play a Major Role in Drug Resistance in Triple-Negative Breast Cancer

2013 ◽  
Vol 12 (4) ◽  
pp. 491-498 ◽  
Author(s):  
Shuping Yin ◽  
Liping Xu ◽  
R. Daniel Bonfil ◽  
Sanjeev Banerjee ◽  
Fazlul H. Sarkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Initiating Cells

Apoptosis, Chemoresistance, and Breast Cancer: Insights From the MCF-7 Cell Model System

2003 ◽  
Vol 228 (9) ◽  
pp. 995-1003 ◽  
Author(s):  
Rebecca Simstein ◽  
Matthew Burow ◽  
Amanda Parker ◽  
Christopher Weldon ◽  
Barbara Beckman
Keyword(s):  
Breast Cancer ◽  
Cell Model ◽  
Model System ◽  
Cell Model System ◽  
Mcf 7

scholarly journals Evidence for Phenotypic Plasticity in Aggressive Triple-Negative Breast Cancer: Human Biology Is Recapitulated by a Novel Model System

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45684 ◽  
Author(s):  
Nicholas C. D’Amato ◽  
Julie H. Ostrander ◽  
Michelle L. Bowie ◽  
Christopher Sistrunk ◽  
Alexander Borowsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phenotypic Plasticity ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Model System ◽  
Human Biology ◽  
Novel Model

scholarly journals Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer

2016 ◽  
Vol 77 (2) ◽  
pp. 566-578 ◽  
Author(s):  
Vikram B. Wali ◽  
Casey G. Langdon ◽  
Matthew A. Held ◽  
James T. Platt ◽  
Gauri A. Patwardhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Drug Screening ◽  
Triple Negative ◽  
Combination Therapies
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