<i>Cripto-1</i> as a novel therapeutic target for triple negative breast cancer

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

doi:10.18632/oncotarget.4182

Cited by 56 publications

(54 citation statements)

References 52 publications

(83 reference statements)

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“…Up to now, extensive literatures documented the efficacy of distinct delivery systems, such as the liposome system, nano-partical system, and polyetherimide (PEI) system, and so on, in cancer gene therapy 6, 47, 48. However, related documents on the potential value of targeted expression of interesting genes using specific gene promoter, such as tumor suppressor, in cancer gene therapy is still scare.…”

Section: Discussionmentioning

confidence: 99%

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

Chen

Zhao

et al. 2017

Molecular Therapy - Nucleic Acids

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Targeted expression of gene technique is an important therapeutic strategy for lung cancer. MicroRNA-7 has been well documented as a promising tumor suppressor but never been test in specific gene-promoter-targeted expression in cancer gene therapy. Here, we first evaluated the efficacy of miR-7 expression operated by the promoter of TTF-1, a lineage-specific oncogene in lung cancer, in vitro using an eukaryotic vector of TTF-1-promoter-operated expression of miR-7 (termed as p-T-miR-7). Interestingly, using a nude mice model, the growth and metastasis of human lung cancer cells in vivo were significantly reduced in remote hypodermic injection of the p-T-miR-7 group, accompanied by increased expression of miR-7 and reduced transduction of the Akt and Erk pathway in situ. Mechanism aspect, global gene expression analysis showed that downregulation of NDUFA4, a novel target of miR-7, contributed to the effects of miR-7 expression operated by TTF-1 promoter on the growth and metastasis of human lung cancer cells, as well as altered transduction of the Akt and Erk pathway. Finally, there was no significant difference in weight or histopathology of other organs. These data provided a basis for development of novel modality of miRNA-based targeted expression therapy against clinical lung cancer.

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Section: Discussionmentioning

confidence: 99%

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

Chen

Zhao

et al. 2017

Molecular Therapy - Nucleic Acids

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“…The cells were maintained in DMEM 1Â (Gibco by Life Technologies), supplemented with 10% FBS and 100 U/mL penicillin, and 100 mg/mL streptomycin at 37 C in 5% CO 2 . The JygMC(A) cells were transduced by a lentivirus promoter containing a fusion of firefly luciferase and eGFP reporters (pFUGW FerH ffLuc2 neo eGFP) as documented previously (16). R, S-sulforaphane was purchased from LKT Laboratories, Inc., dissolved in 0.9% NaCl solution, and stored at À20 C under N 2 gas.…”

Section: Cell Lines and Reagentsmentioning

confidence: 99%

Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

Castro

Rangel

Merchant

et al. 2019

Cancer Prevention Research

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Triple-negative breast cancer (TNBC) represents the poorest prognosis among all of breast cancer subtypes with no currently available effective therapy. In this study, we hypothesized that sulforaphane, a dietary component abundant in broccoli and its sprouts, can inhibit malignant cell proliferation and tumor sphere formation of cancer stem-like cells (CSC) in TNBC. CSC population was isolated using FACS analysis with the combined stem cell surface markers, CD44 þ /CD24 À / CD49f þ. The effect of sulforaphane on a stem-related embryonic oncogene CRIPTO-1/TDGF1 (CR1) was evaluated via ELISA. In vivo, BalbC/nude mice were supplemented with sulforaphane before and after TNBC cell inoculation (daily intraperitoneal injection of 50 mg sulforaphane/kg for 5 and 3 weeks, respectively), and the effects of sulforaphane during mamma-ry tumor initiation and growth were accessed with NanoString gene analysis. We found that sulforaphane can inhibit cell proliferation and mammosphere formation of CSCs in TNBC. Further analysis of gene expression in these TNBC tumor cells revealed that sulforaphane significantly decreases the expression of cancer-specific CR1, CRIPTO-3/TDGF1P3 (CR3, a homologue of CR1), and various stem cell markers including Nanog, aldehyde dehydrogenase 1A1 (ALDH1A1), Wnt3, and Notch4. Our results suggest that sulforaphane may control the malignant proliferation of CSCs in TNBC via Cripto-mediated pathway by either suppressing its expression and/or by inhibiting Cripto/Alk4 protein complex formation. Thus, the use of sulforaphane for chemoprevention of TNBC is plausible and warrants further clinical evaluation.

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“…1 Triple negative breast cancer (TNBC)-defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression-is associated with aggressive growth, a high rate of metastasis, and the poorest prognosis of all breast cancer sub-types. [2][3][4] Due to the lack of therapeutic targets, TNBC is unresponsive to typical endocrine therapies and HER2-targeted therapy. 2 The treatment of patients with TNBC remains a great clinical challenge.…”

Section: Introductionmentioning

confidence: 99%

Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer

et al. 2018

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Triple negative breast cancer (TNBC), which constitutes 10%-20% of all breast cancers, is associated with aggressive progression, a high rate of metastasis, and poor prognosis. The treatment of patients with TNBC remains a great clinical challenge. Preclinical reports support the combination immunotherapy of cancer vaccines and immune checkpoint blockades in non-immunogenic tumors. In this study, we constructed nanoparticles (NPs) to deliver an mRNA vaccine encoding tumor antigen MUC1 to dendritic cells (DCs) in lymph nodes to activate and expand tumor-specific T cells. An anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) monoclonal antibody was combined with the mRNA vaccine to enhance the anti-tumor benefits. In vivo studies demonstrated that the NP-based mRNA vaccine, targeted to mannose receptors on DCs, could successfully express tumor antigen in the DCs of the lymph node; that the NP vaccine could induce a strong, antigen-specific, in vivo cytotoxic T lymphocyte response against TNBC 4T1 cells; and that combination immunotherapy of the vaccine and anti-CTLA-4 monoclonal antibody could significantly enhance anti-tumor immune response compared to the vaccine or monoclonal antibody alone. These data support both the NP as a carrier for delivery of mRNA vaccine and a potential combination immunotherapy of the NP-based mRNA vaccine and the CTLA-4 inhibitor for TNBC.

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

Cited by 56 publications

References 52 publications

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer

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