A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model |
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| Authors: | Adriana Jiménez Adolfo López-Ornelas Enrique Estudillo Lorenza González-Mariscal Rosa O González José Segovia |
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| Institution: | 1. Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del IPN, México D.F., Mexico;2. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN # 2508, México D.F. 07300, Mexico;3. Departamento de Matemáticas, Universidad Autónoma Metropolitana-Iztapalapa, México D.F., Mexico |
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| Abstract: | We previously demonstrated the capacity of GAS1 (Growth Arrest Specific 1) to inhibit the growth of gliomas by blocking the GDNF–RET signaling pathway. Here, we show that a soluble form of GAS1 (tGAS1), decreases the number of viable MDA MB 231 human breast cancer cells, acting in both autocrine and paracrine manners when secreted from producing cells. Moreover, tGAS1 inhibits the growth of tumors implanted in female nu/nu mice through a RET-independent mechanism which involves interfering with the Artemin (ARTN)-GFRα3-(GDNF Family Receptor alpha 3) mediated intracellular signaling and the activation of ERK. In addition, we observed that the presence of tGAS1 reduces the vascularization of implanted tumors, by preventing the migration of endothelial cells. The present results support a potential adjuvant role for tGAS1 in the treatment of breast cancer, by detaining tumor growth and inhibiting angiogenesis. |
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| Keywords: | ARTN Artemin EGFP enhanced green fluorescent protein ERK extracellular-signal regulated kinase GAS1 Growth Arrest Specific 1 GDNF glial derived neurotrophic factor GFRα GDNF family receptor alpha RET rearranged during transfection tGAS1 soluble form of GAS1 VE-Cadherin vascular endothelial cadherin VEGF vascular endothelial growth factor |
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