Elongator drives breast cancer initiation and metastasis formation

Elongator complex functions in diverse cellular processes, such as protein acetylation and tRNA modification, and is essential for cell migration and neuronal differentiation. Although it is well established that tumor development involves modifications of acetylation-deacetylation dynamics as well as changes in protein translation, the role of Elongator in tumor initiation and invasion remains to be studied. Breast cancer is amongst the most common cause of cancer-related deaths in women, and the majority of them involved metastasis dissemination. In vitro, the inactivation of elongator affects the migration and the clonogenic potential of breast cancer cells. In vivo, expression of the ELP1 and Elp3 subunits is elevated over tumor development and in lung metastasis of PyMT-MMTV breast cancer mice. To address the role of elongator in tumor development in vivo, we generated a mouse model in which the catalytic subunit Elp3 is specifically invalidated in the mammary epithelium (Elp3ΔMEC), that we crossed with the PyMT-MMTV model of breast cancer. Elp3 ablation in the mammary epithelium of the PyMT mice caused a delay in primary tumor initiation and reduced metastasis to distal sites. Moreover, PyMT tumor cells formed less mammospheres in the absence of Elp3. Together, our data demonstrate that elongator complex is a key actor in breast cancer initiation and dissemination.