Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer

2015 ◽  
Vol 469 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ellappan Babu ◽  
Yangzom D. Bhutia ◽  
Sabarish Ramachandran ◽  
Jaya P. Gnanaprakasam ◽  
Puttur D. Prasad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Mouse Models ◽  
Therapeutic Target ◽  
Tumour Growth ◽  
Mammalian Target Of Rapamycin ◽  
Amino Acid Transporter ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Acid Transporter

Deletion of the amino acid transporter Slc6a14 in mice suppresses tumour growth in spontaneous models of breast cancer via interference with mammalian target of rapamycin (mTOR) pathway; this indicates an obligatory role for SLC6A14 in breast cancer, highlighting its potential as a therapeutic target.

scholarly journals The amino acid transporter Slc7a5 regulates the mTOR pathway and is required for granule cell development

2020 ◽  
Vol 29 (18) ◽  
pp. 3003-3013 ◽  
Author(s):  
Aidan M Sokolov ◽  
Jennie C Holmberg ◽  
David M Feliciano
Keyword(s):  
Amino Acid ◽  
Granule Cell ◽  
Neural Development ◽  
Mammalian Target Of Rapamycin ◽  
Amino Acid Transporter ◽  
Mtor Pathway ◽  
Normal Brain ◽  
Mtor Inhibition ◽  
Pathway Activity ◽  
Acid Transporter

Abstract Pathogenic mutations in the solute carrier family 7 member 5 (SLC7A5) gene, which encodes an amino acid transporter cause microcephaly and seizures, yet the mechanisms responsible for these phenotypes are unclear. Models have demonstrated that Slc7a5 deletion is embryonic lethal and that these embryos lack a fully formed telencephalon. This phenotype is similar to that of mammalian target of rapamycin (mTOR) protein kinase deletion or mTOR inhibition. Notably, in many cells, Slc7a5 import of amino acids is required to maintain mTOR activity. Slc7a5 is present within neurogenic regions during embryogenesis, is found in cultured neurons and can modulate neuronal electrophysiological properties. However, Slc7a5 is also highly expressed within endothelial cells of the blood–brain barrier where removal in conditional mice leads to severe behavioral defects and non-cell autonomous changes in neurons. Therefore, the extent that neural Slc7a5 is required for development is unclear. Here, subventricular zone neural stem cells that generate olfactory bulb granule cell neurons were electroporated with SLC7A5 or Slc7a5 short hairpin RNA encoding plasmids. Although early phases of neural development were unaltered, Slc7a5 knockdown effected late phases of GC dendrite maturation and survival. Slc7a5 knockdown also decreased mTOR pathway activity. Ras homolog enriched in brain, an mTOR activator, rescued the effect of Slc7a5 knockdown on mTOR pathway activity and dendrite arbors. The data presented here demonstrate that Slc7a5 is required for GC mTOR pathway activity, maturation and survival, which may help explain why Slc7a5 mutations prevent normal brain development and function.

scholarly journals Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer

2020 ◽  
pp. jclinpath-2020-206457
Author(s):  
Masaaki Ichinoe ◽  
Tetuo Mikami ◽  
Nobuyuki Yanagisawa ◽  
Tsutomu Yoshida ◽  
Kiyomi Hana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Invasive Breast Cancer ◽  
Poor Prognosis ◽  
Growth Factor Receptor ◽  
Amino Acid Transporter ◽  
Breast Cancers ◽  
Non Invasive ◽  
Invasive Tumour ◽  
Acid Transporter

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

scholarly journals Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer

2021 ◽  
Author(s):  
Sasagu Kurouzmi ◽  
Kyoichi Kaira ◽  
Hiroshi Matsumoto ◽  
Masafumi Kurosumi ◽  
Takehiko Yokobori ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Histological Grade ◽  
Amino Acid Transporter ◽  
Breast Cancer Patients ◽  
Poor Prognostic Factor ◽  
Luminal B ◽  
Acid Transporter

Abstract PURPOSE: L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression. METHODS: LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationship between LAT1 expression and the patients’ outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed.RESULTS: High LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased tumor-infiltrating lymphocytes, and programmed death ligand 1 positivity. Among the ER-positive and human epidermal growth factor 2-negative type cases, high LAT1 was an independent indicator of poor outcomes (hazard ratio (HR) = 2.97; 95% confidence interval (CI), 1.16–7.62; p = 0.023). Moreover, high LAT1 expression was an independent poor prognostic factor in luminal B-like breast cancer with aggressive features (HR = 3.39; 95% CI, 1.35–8.52; p = 0.0094).CONCLUSIONS: High LAT1 expression identified a subgroup of invasive breast cancer characterized by aggressive behavior and high tumor immunoreaction. Our findings suggest that LAT1 might be a candidate therapeutic target for breast cancer patients, particularly those with luminal B-like type breast cancer.

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