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

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11910-11929
Number of pages20
JournalOncotarget
Volume6
Issue number14
DOIs
Publication statusPublished - 01-01-2015
Externally publishedYes

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Triple Negative Breast Neoplasms
MicroRNAs
Lung
Neoplasms
Adenocarcinoma
Clustered Regularly Interspaced Short Palindromic Repeats
Breast Neoplasms
Neoplasm Metastasis
Laser Capture Microdissection
Therapeutics
Embryonic Stem Cells
Messenger RNA
Growth

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Castro, N. P., Fedorova-Abrams, N. D., Merchant, A. S., Rangel, M. C., Nagaoka, T., Karasawa, H., ... 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
Castro, Nadia P. ; Fedorova-Abrams, Natalie D. ; Merchant, Anand S. ; Rangel, Maria Cristina ; Nagaoka, Tadahiro ; Karasawa, Hideaki ; Klauzinska, Malgorzata ; Hewitt, Stephen M. ; Biswas, Kajal ; Sharan, Shyam K. ; Salomon, David S. / Cripto-1 as a novel therapeutic target for triple negative breast cancer. In: Oncotarget. 2015 ; Vol. 6, No. 14. pp. 11910-11929.
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Castro, NP, Fedorova-Abrams, ND, Merchant, AS, Rangel, MC, Nagaoka, T, Karasawa, H, Klauzinska, M, Hewitt, SM, Biswas, K, Sharan, SK & Salomon, DS 2015, 'Cripto-1 as a novel therapeutic target for triple negative breast cancer', Oncotarget, vol. 6, no. 14, pp. 11910-11929. https://doi.org/10.18632/oncotarget.4182

Cripto-1 as a novel therapeutic target for triple negative breast cancer. / Castro, Nadia P.; Fedorova-Abrams, Natalie D.; Merchant, Anand S.; Rangel, Maria Cristina; Nagaoka, Tadahiro; Karasawa, Hideaki; Klauzinska, Malgorzata; Hewitt, Stephen M.; Biswas, Kajal; Sharan, Shyam K.; Salomon, David S.

In: Oncotarget, Vol. 6, No. 14, 01.01.2015, p. 11910-11929.

Research output: Contribution to journalArticle

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Castro NP, Fedorova-Abrams ND, Merchant AS, Rangel MC, Nagaoka T, Karasawa H et al. Cripto-1 as a novel therapeutic target for triple negative breast cancer. Oncotarget. 2015 Jan 1;6(14):11910-11929. https://doi.org/10.18632/oncotarget.4182