Subcellular localization of mRNAs is regulated by RNA-protein interactions. Here, we show that introduction of a reporter mRNA with the 3'UTR of β-actin mRNA competes with endogenous mRNAs for binding to ZBP1 in adult sensory neurons. ZBP1 is needed for axonal localization of β-actin mRNA, and introducing GFP with the 3'UTR of β-actin mRNA depletes axons of endogenous β-actin and GAP-43 mRNAs and attenuates both in vitro and in vivo regrowth of severed axons. Consistent with limited levels of ZBP1 protein in adult neurons, mice heterozygous for the ZBP1 gene are haploinsufficient for axonal transport of β-actin and GAP-43 mRNAs and for regeneration of peripheral nerve. Exogenous ZBP1 can rescue the RNA transport deficits, but the axonal growth deficit is only rescued if the transported mRNAs are locally translated. These data support a direct role for ZBP1 in transport and translation of mRNA cargos in axonal regeneration in vitro and in vivo.

Purpose L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. Methods LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[ 18 F]fluorocyclobutane-1-carboxylic acid (anti-[ 18 F]FACBC) PET was assessed for its diagnostic biomarker potential. Results Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[ 18 F]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. Conclusions The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[ 18 F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

We evaluate National Cancer Institute (NCI) funding distribution to the most common cancers, considering their respective public health burdens and explore associations between funding and racial/ethnic burden of disease. The NCI’s Surveillance, Epidemiology and End Results (SEER), United States Cancer Statistics (USCS) database, and Funding Statistics were used to calculate funding-to-lethality (FTL) scores. Breast and prostate cancer had the 1st (179.65) and 2nd (128.90) highest FTL scores while esophagus and stomach cancer ranked 18th (2.12) and 19th (1.78). We evaluated whether there were differences between the FTL and cancer incidence and/or mortality within individual racial/ethnic groups. NCI funding correlated highly with cancers afflicting a higher proportion of non-Hispanic whites (Spearman Correlation Coefficient = 0.84, p < .001). Correlation was stronger for incidence than mortality. These data reveal that funding across cancer sites is not concordant with lethality and that cancers with high incidence among racial/ethnic minorities receive lower funding.

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