Clinical Role of ASCT2 (SLC1A5) in KRAS-Mutated Colorectal Cancer.
Int J Mol Sci
; 18(8)2017 Jul 27.
Article
in En
| MEDLINE
| ID: mdl-28749408
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Minor Histocompatibility Antigens
/
Proto-Oncogene Proteins p21(ras)
/
Amino Acid Transport System ASC
/
Mutation
Type of study:
Prognostic_studies
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
Int J Mol Sci
Year:
2017
Document type:
Article
Affiliation country:
Japan