Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer
Abstract Background The amino acid transporter SLC6A14, which transports 18 of the 20 proteinogenic amino acids, is too low to be detected in healthy normal tissues but is significantly increased in some solid cancers. However, little is known about the roles of SLC6A14 in colorectal cancer (CRC). M...
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| Format: | Article |
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BMC
2022-07-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09935-0 |
| _version_ | 1811222880346701824 |
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| author | Ying Lu Ziting Jiang Kaijing Wang Shanshan Yu Chongbo Hao Zuan Ma Xuelian Fu Ming Qing Qin Zengguang Xu Lieying Fan |
| author_facet | Ying Lu Ziting Jiang Kaijing Wang Shanshan Yu Chongbo Hao Zuan Ma Xuelian Fu Ming Qing Qin Zengguang Xu Lieying Fan |
| author_sort | Ying Lu |
| collection | DOAJ |
| description | Abstract Background The amino acid transporter SLC6A14, which transports 18 of the 20 proteinogenic amino acids, is too low to be detected in healthy normal tissues but is significantly increased in some solid cancers. However, little is known about the roles of SLC6A14 in colorectal cancer (CRC). Methods The mRNA and protein levels of SLC6A14 were detected using TCGA database, real-time polymerase chain reaction, western blot, and tissue microarrays, respectively. Amino acids concentration was determined by LC-MS/MS. Cell proliferation and apoptosis were determined using MTT assay and flow cytometry. Transwell invasion assay and wound healing assay were employed to analyze cell migration and invasion. The protein levels of Akt-mTOR signaling pathway and MMPs proteins were detected by western blot. Results Both of the mRNA and protein levels of SLC6A14 were upregulated in CRC tissues, and the protein levels of SLC6A14 were closely related to the tumor cells differentiation: the higher the expression of SLC6A14 was, the poorer the differentiation of the tumor cells was. Further knockdown SLC6A14 with siRNA or treatment with α-MT in CRC cell lines reduced cell proliferation and migration in vitro and inhibited xenograft tumor growth in vivo. Mechanistically, SLC6A14 was demonstrated to regulate the expression and phosphorylation of Akt-mTOR, which mediates the promoting tumor growth function of SLC6A14. Blockade of SLC6A14 with α-MT inhibited the activation of mTOR signaling. Conclusion SLC6A14 was upregulated in CRC and could promote tumor progression by activating the Akt-mTOR signaling pathway, which may serve as an effective molecular target for the treatment of CRC. |
| first_indexed | 2024-04-12T08:23:19Z |
| format | Article |
| id | doaj.art-a82f3eec58b243e996d6f3e481bb1759 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T08:23:19Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-a82f3eec58b243e996d6f3e481bb17592022-12-22T03:40:30ZengBMCBMC Cancer1471-24072022-07-0122111610.1186/s12885-022-09935-0Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal CancerYing Lu0Ziting Jiang1Kaijing Wang2Shanshan Yu3Chongbo Hao4Zuan Ma5Xuelian Fu6Ming Qing Qin7Zengguang Xu8Lieying Fan9Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityDepartment of Endoscopy, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan UniversityResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityDepartment of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tongji UniversityResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji UniversityDepartment of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tongji UniversityAbstract Background The amino acid transporter SLC6A14, which transports 18 of the 20 proteinogenic amino acids, is too low to be detected in healthy normal tissues but is significantly increased in some solid cancers. However, little is known about the roles of SLC6A14 in colorectal cancer (CRC). Methods The mRNA and protein levels of SLC6A14 were detected using TCGA database, real-time polymerase chain reaction, western blot, and tissue microarrays, respectively. Amino acids concentration was determined by LC-MS/MS. Cell proliferation and apoptosis were determined using MTT assay and flow cytometry. Transwell invasion assay and wound healing assay were employed to analyze cell migration and invasion. The protein levels of Akt-mTOR signaling pathway and MMPs proteins were detected by western blot. Results Both of the mRNA and protein levels of SLC6A14 were upregulated in CRC tissues, and the protein levels of SLC6A14 were closely related to the tumor cells differentiation: the higher the expression of SLC6A14 was, the poorer the differentiation of the tumor cells was. Further knockdown SLC6A14 with siRNA or treatment with α-MT in CRC cell lines reduced cell proliferation and migration in vitro and inhibited xenograft tumor growth in vivo. Mechanistically, SLC6A14 was demonstrated to regulate the expression and phosphorylation of Akt-mTOR, which mediates the promoting tumor growth function of SLC6A14. Blockade of SLC6A14 with α-MT inhibited the activation of mTOR signaling. Conclusion SLC6A14 was upregulated in CRC and could promote tumor progression by activating the Akt-mTOR signaling pathway, which may serve as an effective molecular target for the treatment of CRC.https://doi.org/10.1186/s12885-022-09935-0SLC6A14Colorectal cancerAmino acid transporterα-MethyltryptophanmTOR |
| spellingShingle | Ying Lu Ziting Jiang Kaijing Wang Shanshan Yu Chongbo Hao Zuan Ma Xuelian Fu Ming Qing Qin Zengguang Xu Lieying Fan Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer BMC Cancer SLC6A14 Colorectal cancer Amino acid transporter α-Methyltryptophan mTOR |
| title | Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer |
| title_full | Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer |
| title_fullStr | Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer |
| title_full_unstemmed | Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer |
| title_short | Blockade of the amino acid transporter SLC6A14 suppresses tumor growth in colorectal Cancer |
| title_sort | blockade of the amino acid transporter slc6a14 suppresses tumor growth in colorectal cancer |
| topic | SLC6A14 Colorectal cancer Amino acid transporter α-Methyltryptophan mTOR |
| url | https://doi.org/10.1186/s12885-022-09935-0 |
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