SLC38A1 drives malignant progression of hepatocellular carcinoma by activating PI3K/AKT signaling via enhanced glutamine uptake
10.16016/j.2097-0927.202508018
- VernacularTitle:SLC38A1通过促进谷氨酰胺摄取激活PI3K/AKT信号通路驱动肝细胞癌恶性进展
- Author:
Yuanyuan YANG
1
;
Ping ZHANG
;
Peng HU
;
Maonian LIU
;
Yanjiao OU
Author Information
1. 重庆海吉亚医院消化疾病中心
- Keywords:
hepatocellular carcinoma;
glutamine;
SLC38A1
- From:
Journal of Army Medical University
2025;47(23):2922-2932
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which SLC38A1 promotes hepatocellular carcinoma(HCC)progression through glutamine transport-mediated activation of the PI3K/AKT signaling pathway.Methods Bioinformatics analysis was employed to assess the correlation between SLC38A1 expression and clinicopathological features/prognosis in HCC patients,with functional enrichment analysis of SLC38A1 conducted.SLC38A1 was silenced or over expressed via transfection in Huh-7 cells,with glutamine inhibited using DRP-104 and the PI3K/AKT pathway suppressed using LY294002.Cell viability,proliferation,migration,invasion,and glutamine concentration were evaluated using CCK-8,EdU staining,scratch wound healing assay,Transwell chamber assay,and glutamine assay kits,respectively.PI3K/AKT pathway activity was assessed by Western blotting.Results SLC38A1 mRNA and protein levels were significantly higher in HCC tumor tissues than in adjacent normal tissues(P<0.05).HCC patients with high SLC38A1 expression exhibited significantly lower overall survival than those with low expression(P<0.05).SLC38A1 expression correlated significantly with pathologic T-stage(pT),N-stage(pN),M-stage(pM),survival status,and immune infiltration in HCC patients(P<0.05).SLC38A1 silencing markedly reduced glutamine uptake in HCC cells(P<0.001),suppressing cell viability,proliferation,migration,invasion,and PI3K/AKT pathway activity(P<0.001).Conversely,SLC38A1 overexpression promoted proliferation,migration,invasion,and PI3K/AKT activation(P<0.001).DRP-104-mediated glutamine inhibition suppressed HCC cell malignancy and PI3K/AKT signaling while abolishing the oncogenic effects of SLC38A1 overexpression(P<0.001).PI3K/AKT pathway inhibition blocked the pro-tumorigenic effects of SLC38A1 overexpression(P<0.001).Conclusion SLC38A1 promotes proliferation,migration,and invasion in HCC by activating the PI3K/AKT pathway through enhanced glutamine transport.
