The CXCR4-LASP1-eIF4F Axis Promotes Translation of Oncogenic Proteins in Triple-Negative Breast Cancer Cells

In this study, we confirm our initial findings from the proteomic screen and demonstrate that LASP1 can interact with both eIF4A and eIF4B. Importantly, the LASP1-eIF4A and LASP1-eIF4B interaction is shown to be CXCL12-dependent. In addition, the ability of CXCR4 to impact the phosphorylation of eIF4F regulatory proteins is provided. Taken together, we hypothesize that activation of CXCR4 can promote eIF4F complex formation and activity through LASP1 and cell signaling. As a result, the translation of oncogenic proteins is promoted thereby mediating an invasive and metastatic phenotype commonly associated with CXCR4. Materials and Methods Bioinformatics Analysis To determine the significance of the CXCR4-LASP1-eIF4A/B axis in patient tissues, gene expression data was obtained and analyzed using Oncomine™ (54–56). Settings in the program were limited to a “cancer vs. normal analysis” and “breast cancer.” Data from two representative datasets are shown. Datasets include: Radvanyi Breast (PNAS, 08/02/2005) and TCGA Breast (The Cancer Genome Atlas, 09/02/2011). Box and whisker plots of the log2 median centered ratio for each cancer subtype were generated in the “R” statistical package (version 3.5.1) and the generated graphics were modified in Inkscape (version 0.92.3). Cell Culture MDA-MB-231 human breast cancer cells (MDA-MB-231: ATCC® HTB-26™, Manassas, VA) were previously sorted for high cell...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research