Nodal expression in triple-negative breast cancer: Cellular effects of its inhibition following doxorubicin treatment
| Autor: | Grace S. Chandler, Thomas M. Bodenstine, Naira V. Margaryan, Mary J.C. Hendrix, Luigi Strizzi, Nida Ahmed, Alina Gilgur, Elisabeth A. Seftor, Matthew Hyser, David W. Reed, Janis Atkinson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nodal signaling Estrogen receptor Cell Biology Biology medicine.disease Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Breast cancer Cancer stem cell 030220 oncology & carcinogenesis Cancer cell medicine Cancer research Doxorubicin Molecular Biology Triple-negative breast cancer Developmental Biology medicine.drug |
| Zdroj: | Cell Cycle. 15:1295-1302 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.1080/15384101.2016.1160981 |
| Popis: | Triple-negative breast cancer (TNBC) represents an aggressive cancer subtype characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The independence of TNBC from these growth promoting factors eliminates the efficacy of therapies which specifically target them, and limits TNBC patients to traditional systemic neo/adjuvant chemotherapy. To better understand the growth advantage of TNBC - in the absence of ER, PR and HER2, we focused on the embryonic morphogen Nodal (associated with the cancer stem cell phenotype), which is re-expressed in aggressive breast cancers. Most notably, our previous data demonstrated that inhibition of Nodal signaling in breast cancer cells reduces their tumorigenic capacity. Furthermore, inhibiting Nodal in other cancers has resulted in improved effects of chemotherapy, although the mechanisms for this remain unknown. Thus, we hypothesized that targeting Nodal in TNBC cells in combination with conventional chemotherapy may improve efficacy and represent a potential new strategy. Our preliminary data demonstrate that Nodal is highly expressed in TNBC when compared to invasive hormone receptor positive samples. Treatment of Nodal expressing TNBC cell lines with a neutralizing anti-Nodal antibody reduces the viability of cells that had previously survived treatment with the anthracycline doxorubicin. We show that inhibiting Nodal may alter response mechanisms employed by cancer cells undergoing DNA damage. These data suggest that development of therapies which target Nodal in TNBC may lead to additional treatment options in conjunction with chemotherapy regimens - by altering signaling pathways critical to cellular survival. |
| Databáze: | OpenAIRE |
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