A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model

作者：Jimenez Adriana; Lopez Ornelas Adolfo; Estudillo Enrique; Gonzalez Mariscal Lorenza; Gonzalez Rosa O; Segovia Jose^*

来源：Experimental Cell Research, 2014, 327(2): 307-317.

DOI：10.1016/j.yexcr.2014.06.016

• Growth Arrest Specific 1
• tGAS1
• Breast cancer
• Artemin
• ERK1/2
• Angiogenesis

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)-GFR alpha 3-(GDNE 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.

• 出版日期2014-10-1