Cripto-1 as a novel therapeutic target for triple negative breast cancer

Autor: Maria Cristina Rangel, Natalie D. Fedorova-Abrams, Tadahiro Nagaoka, David S. Salomon, Anand S. Merchant, Shyam K. Sharan, Nadia P. Castro, Malgorzata Klauzinska, Kajal Biswas, Hideaki Karasawa, Stephen M. Hewitt
Předmět:
Pathology
medicine.medical_specialty
Epithelial-Mesenchymal Transition
mouse model
Fluorescent Antibody Technique
Mice
Nude
Triple Negative Breast Neoplasms
Laser Capture Microdissection
Biology
Cripto
Polymerase Chain Reaction
Gene Knockout Techniques
Mice
Breast cancer
Cell Line
Tumor
medicine
In Situ Nick-End Labeling
Animals
Epithelial–mesenchymal transition
notch4
Triple-negative breast cancer
Microdissection
Laser capture microdissection
Oligonucleotide Array Sequence Analysis
Mice
Inbred BALB C
Membrane Glycoproteins
Epidermal Growth Factor
cripto-1
Mammary Neoplasms
Experimental
medicine.disease
Immunohistochemistry
Neoplasm Proteins
Cell Transformation
Neoplastic
epithelial-mesenchymal plasticity
Oncology
Cancer research
triple-negative breast cancer
Adenocarcinoma
Female
Priority Research Paper
Zdroj: ResearcherID
Oncotarget
Popis: Triple-negative breast cancer (TNBC) presents the poorest prognosis among the breast cancer subtypes and no current standard therapy. Here, we performed an in-depth molecular analysis of a mouse model that establishes spontaneous lung metastasis from JygMC(A) cells. These primary tumors resembled the triple-negative breast cancer (TNBC) both phenotypically and molecularly. Morphologically, primary tumors presented both epithelial and spindle-like cells but displayed only adenocarcinoma-like features in lung parenchyma. The use of laser-capture microdissection combined with Nanostring mRNA and microRNA analysis revealed overexpression of either epithelial and miRNA-200 family or mesenchymal markers in adenocarcinoma and mesenchymal regions, respectively. Cripto-1, an embryonic stem cell marker, was present in spindle-like areas and its promoter showed activity in primary tumors. Cripto-1 knockout by the CRISPR-Cas9 system inhibited tumor growth and pulmonary metastasis. Our findings show characterization of a novel mouse model that mimics the TNBC and reveal Cripto-1 as a TNBC target hence may offer alternative treatment strategies for TNBC.
Databáze: OpenAIRE
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