Next Article in Journal
Host Response Comparison of H1N1- and H5N1-Infected Mice Identifies Two Potential Death Mechanisms
Next Article in Special Issue
PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process
Previous Article in Journal
Sulfur Protects Pakchoi (Brassica chinensis L.) Seedlings against Cadmium Stress by Regulating Ascorbate-Glutathione Metabolism
Previous Article in Special Issue
Tanshinone IIA Inhibits Epithelial-Mesenchymal Transition in Bladder Cancer Cells via Modulation of STAT3-CCL2 Signaling
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle

Clinical Role of ASCT2 (SLC1A5) in KRAS-Mutated Colorectal Cancer

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(8), 1632;
Received: 29 June 2017 / Revised: 24 July 2017 / Accepted: 24 July 2017 / Published: 27 July 2017
(This article belongs to the Special Issue Chemical and Molecular Approach to Tumor Metastases)
PDF [2817 KB, uploaded 27 July 2017]


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. View Full-Text
Keywords: colorectal cancer; KRAS; ASCT2; SLC1A5 colorectal cancer; KRAS; ASCT2; SLC1A5

Graphical abstract

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).

Supplementary material

Printed Edition Available!
A printed edition of this Special Issue is available here.

Share & Cite This Article

MDPI and ACS Style

Toda, K.; Nishikawa, G.; Iwamoto, M.; Itatani, Y.; Takahashi, R.; Sakai, Y.; Kawada, K. Clinical Role of ASCT2 (SLC1A5) in KRAS-Mutated Colorectal Cancer. Int. J. Mol. Sci. 2017, 18, 1632.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top