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Title: Clinical role of ASCT2 (SLC1A5) in KRAS-mutated colorectal cancer
Authors: Toda, Kosuke
Nishikawa, Gen
Iwamoto, Masayoshi
Itatani, Yoshiro  kyouindb  KAKEN_id
Takahashi, Ryo
Sakai, Yoshiharu
Kawada, Kenji
Author's alias: 岩本, 哲好
板谷, 喜朗
高橋, 亮
坂井, 義治
河田, 健二
Keywords: colorectal cancer
KRAS
ASCT2
SLC1A5
Issue Date: 1-Aug-2017
Publisher: MDPI AG
Journal title: International Journal of Molecular Sciences
Volume: 18
Issue: 8
Thesis number: 1632
Abstract: Mutation in the KRAS gene induces prominent metabolic changes. We have recently reported that KRAS mutations in colorectal cancer (CRC) cause alterations in amino acid metabolism. However, it remains to be investigated which amino acid transporter can be regulated by mutated KRAS in CRC. Here, we performed a screening of amino acid transporters using quantitative reverse-transcription polymerase chain reaction (RT-PCR) and then identified that ASCT2 (SLC1A5) was up-regulated through KRAS signaling. Next, immunohistochemical analysis of 93 primary CRC specimens revealed that there was a significant correlation between KRAS mutational status and ASCT2 expression. In addition, the expression level of ASCT2 was significantly associated with tumor depth and vascular invasion in KRAS-mutant CRC. Notably, significant growth suppression and elevated apoptosis were observed in KRAS-mutant CRC cells upon SLC1A5-knockdown. ASCT2 is generally known to be a glutamine transporter. Interestingly, SLC1A5-knockdown exhibited a more suppressive effect on cell growth than glutamine depletion. Furthermore, SLC1A5-knockdown also resulted in the suppression of cell migration. These results indicated that ASCT2 (SLC1A5) could be a novel therapeutic target against KRAS-mutant CRC.
Rights: © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
URI: http://hdl.handle.net/2433/233076
DOI(Published Version): 10.3390/ijms18081632
PubMed ID: 28749408
Appears in Collections:Journal Articles

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