TY - JOUR
T1 - Cripto-1 as a novel therapeutic target for triple negative breast cancer
AU - Castro, Nadia P.
AU - Fedorova-Abrams, Natalie D.
AU - Merchant, Anand S.
AU - Rangel, Maria Cristina
AU - Nagaoka, Tadahiro
AU - Karasawa, Hideaki
AU - Klauzinska, Malgorzata
AU - Hewitt, Stephen M.
AU - Biswas, Kajal
AU - Sharan, Shyam K.
AU - Salomon, David S.
PY - 2015
Y1 - 2015
N2 - 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 triplenegative 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.
AB - 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 triplenegative 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.
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U2 - 10.18632/oncotarget.4182
DO - 10.18632/oncotarget.4182
M3 - Article
C2 - 26059540
AN - SCOPUS:84931360117
SN - 1949-2553
VL - 6
SP - 11910
EP - 11929
JO - Oncotarget
JF - Oncotarget
IS - 14
ER -