Abstract P1-05-23: Blockade of mTORC1 decreases CXCR4-mediated migration and metastasis

Abstract

Abstract Tumor cells can co-opt the promigratory activity of chemokines and their cognate G protein–coupled receptors (GPCRs) to metastasize to regional lymph nodes or distant organs. Indeed, the migration toward SDF-1 (stromal cell–derived factor 1) of tumor cells bearing CXCR4 [chemokine (C-X-C motif) receptor 4] has been implicated in the lymphatic and organ-specific metastasis of various human malignancies, including breast cancer. The downstream mechanisms of CXCR4-mediated migration are not fully elucidated. The study of the precise signaling pathways involved in cell migration and metastasis in each tumor type may help identify novel therapeutic targets for improving cancer therapy. Here we show that blockade of mTOR complex 1 (mTORC1) by Rapamycin or knocking down Raptor decreases CXCR4-Gαi mediated cell migration. Moreover, using a spontaneous lymph node metastasis model, we were able to show that pharmacological blockade of mTORC1 decreases lymph node metastasis in vivo. Taken together our data suggest that Rapamycin, a FDA-approved drug, could be beneficial to prevent tumor cells spreading from the primary tumor and metastasize. Molecular events underlying the effects of Rapamycin on CXCR4-induced migration will be presented. This research was supported [in part] by the Intramural Research Program of the NIH, NIDCR. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-23.