FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1861736197> ?p ?o ?g. }

• W1861736197 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CATumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If we can interfere with the entry of amino acids into tumor cells, we should be able to starve these cells to death. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment. Mammalian cells express ∼40 amino acid transporters, expressed in different combinations and in a cell type-specific manner. Among them, SLC6A14 is unique in that it transports all essential amino acids as well as glutamine, and is expressed only at low levels in normal tissues, but induced in colon cancer and in ER+ breast cancer. Tumor cells in these cancers upregulate SLC6A14 to meet their increased demand for essential amino acids and glutamine, indicating that SLC6A14 drives their “glutamine addiction.” We have now established the potential of this transporter as a drug target for breast cancer treatment using genetic and pharmacologic approaches. For this, we first generated Slc6a14-/- mouse. The Slc6a14 gene is located on X chromosome. Deletion of the gene is not lethal and there is no overt phenotype in hemizygous males (-/y) or in homozygous females (-/-). We then examined the progression of breast cancer in Polyoma middle T antigen (Py-MT) Tg mouse on Slc6a14+/+ and Slc6a14-/- background. Deletion of Slc6a14 markedly suppressed breast cancer and lung metastasis induced by the Py-MT oncogene. We have also identified -methyl-L-tryptophan (-MLT) as a selective blocker of Slc6a14. We investigated the consequences of pharmacologic blockade of Slc6a14 on Py-MT-induced breast cancer with oral administration of -MLT (1 mg/ml in drinking water). The blocker was able to suppress breast cancer to a marked extent. Py-MT-induced breast tumors showed robust upregulation of Slc6a14; however, the tumors also showed upregulation of Slc7a5/Slc3a2, another amino acid transporter. Therefore, we examined the interaction of -MLT with Slc7a5/Slc3a2 and found that while -MLT is a blocker of Slc6a14, it is a transportable substrate for Slc7a5/Slc3a2, demonstrating that only the function of Slc6a14 is selectively blocked by -MLT. We conclude that blockade of Slc6a14 is a viable strategy for treatment of certain specific subtypes of breast cancer (e.g., ER-positive) that are associated with upregulation of the transporter.Citation Format: Babu Ellappan, Yangzom D. Bhutia, Muthusamy Thangaraju, Puttur D. Prasad, Vadivel Ganapathy. Genetic deletion or pharmacologic blockade of the amino acid transporter Slc6a14 in mice suppresses breast cancer induced by Polyoma middle T oncogene. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3928. doi:10.1158/1538-7445.AM2014-3928" @default.
• W1861736197 created "2016-06-24" @default.
• W1861736197 creator A5050131267 @default.
• W1861736197 creator A5073081372 @default.
• W1861736197 creator A5077463491 @default.
• W1861736197 creator A5088440923 @default.
• W1861736197 creator A5091451352 @default.
• W1861736197 date "2014-09-30" @default.
• W1861736197 modified "2023-09-27" @default.
• W1861736197 title "Abstract 3928: Genetic deletion or pharmacologic blockade of the amino acid transporter Slc6a14 in mice suppresses breast cancer induced by Polyoma middle T oncogene" @default.
• W1861736197 doi "https://doi.org/10.1158/1538-7445.am2014-3928" @default.
• W1861736197 hasPublicationYear "2014" @default.
• W1861736197 type Work @default.
• W1861736197 sameAs 1861736197 @default.
• W1861736197 citedByCount "0" @default.
• W1861736197 crossrefType "proceedings-article" @default.
• W1861736197 hasAuthorship W1861736197A5050131267 @default.
• W1861736197 hasAuthorship W1861736197A5073081372 @default.
• W1861736197 hasAuthorship W1861736197A5077463491 @default.
• W1861736197 hasAuthorship W1861736197A5088440923 @default.
• W1861736197 hasAuthorship W1861736197A5091451352 @default.
• W1861736197 hasConcept C104317684 @default.
• W1861736197 hasConcept C121608353 @default.
• W1861736197 hasConcept C127561419 @default.
• W1861736197 hasConcept C149011108 @default.
• W1861736197 hasConcept C168785527 @default.
• W1861736197 hasConcept C2779349466 @default.
• W1861736197 hasConcept C2781018059 @default.
• W1861736197 hasConcept C2781313199 @default.
• W1861736197 hasConcept C29537977 @default.
• W1861736197 hasConcept C502942594 @default.
• W1861736197 hasConcept C515207424 @default.
• W1861736197 hasConcept C54355233 @default.
• W1861736197 hasConcept C55493867 @default.
• W1861736197 hasConcept C86803240 @default.
• W1861736197 hasConcept C96232424 @default.
• W1861736197 hasConceptScore W1861736197C104317684 @default.
• W1861736197 hasConceptScore W1861736197C121608353 @default.
• W1861736197 hasConceptScore W1861736197C127561419 @default.
• W1861736197 hasConceptScore W1861736197C149011108 @default.
• W1861736197 hasConceptScore W1861736197C168785527 @default.
• W1861736197 hasConceptScore W1861736197C2779349466 @default.
• W1861736197 hasConceptScore W1861736197C2781018059 @default.
• W1861736197 hasConceptScore W1861736197C2781313199 @default.
• W1861736197 hasConceptScore W1861736197C29537977 @default.
• W1861736197 hasConceptScore W1861736197C502942594 @default.
• W1861736197 hasConceptScore W1861736197C515207424 @default.
• W1861736197 hasConceptScore W1861736197C54355233 @default.
• W1861736197 hasConceptScore W1861736197C55493867 @default.
• W1861736197 hasConceptScore W1861736197C86803240 @default.
• W1861736197 hasConceptScore W1861736197C96232424 @default.
• W1861736197 hasLocation W18617361971 @default.
• W1861736197 hasOpenAccess W1861736197 @default.
• W1861736197 hasPrimaryLocation W18617361971 @default.
• W1861736197 hasRelatedWork W1572146858 @default.
• W1861736197 hasRelatedWork W1970766774 @default.
• W1861736197 hasRelatedWork W1971205130 @default.
• W1861736197 hasRelatedWork W2006734560 @default.
• W1861736197 hasRelatedWork W2020941639 @default.
• W1861736197 hasRelatedWork W2022039464 @default.
• W1861736197 hasRelatedWork W2042974768 @default.
• W1861736197 hasRelatedWork W2064349177 @default.
• W1861736197 hasRelatedWork W2122844744 @default.
• W1861736197 hasRelatedWork W2131515122 @default.
• W1861736197 hasRelatedWork W2319673266 @default.
• W1861736197 hasRelatedWork W2421484262 @default.
• W1861736197 hasRelatedWork W2477437721 @default.
• W1861736197 hasRelatedWork W2481711178 @default.
• W1861736197 hasRelatedWork W2485342687 @default.
• W1861736197 hasRelatedWork W2886900390 @default.
• W1861736197 hasRelatedWork W2913943097 @default.
• W1861736197 hasRelatedWork W2985657189 @default.
• W1861736197 hasRelatedWork W3046542479 @default.
• W1861736197 hasRelatedWork W61326834 @default.
• W1861736197 isParatext "false" @default.
• W1861736197 isRetracted "false" @default.
• W1861736197 magId "1861736197" @default.
• W1861736197 workType "article" @default.