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

Nadia P. Castro, Natalie D. Fedorova-Abrams, Anand S. Merchant, Maria Cristina Rangel, Tadahiro Nagaoka, Hideaki Karasawa, Malgorzata Klauzinska, Stephen M. Hewitt, Kajal Biswas, Shyam K. Sharan, David S. Salomon

研究成果: Article

36 引用 (Scopus)

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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.

元の言語English
ページ(範囲)11910-11929
ページ数20
ジャーナルOncotarget
6
発行部数14
DOI
出版物ステータスPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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    Castro, N. P., Fedorova-Abrams, N. D., Merchant, A. S., Rangel, M. C., Nagaoka, T., Karasawa, H., Klauzinska, M., Hewitt, S. M., Biswas, K., Sharan, S. K., & Salomon, D. S. (2015). Cripto-1 as a novel therapeutic target for triple negative breast cancer. Oncotarget, 6(14), 11910-11929. https://doi.org/10.18632/oncotarget.4182