biostudies-literatureYao YState Key Laboratory of Oncology in South ChinaSociety of Hong Kong ScholarsResearch Grants Council, University Grants CommitteeUniversity Research Committee, University of Hong KongHarbin Medical UniveristyNatural Science Foundation of Heilongjiang Province251-272https://www.ebi.ac.uk/biostudies/studies/S-EPMC10876205biostudies-literatureUnknown44(2)<h4>Background</h4>Small extracellular vesicles (sEVs) mediate intercellular communication that contributes to hepatocellular carcinoma (HCC) progression via multifaceted pathways. The success of cell entry determines the effect of sEV on recipient cells. Here, we aimed to delineate the mechanisms underlying the uptake of sEV in HCC.<h4>Methods</h4>Macropinocytosis was examined by the ability of cells to internalize dextran and sEV. Macropinocytosis was analyzed in Na(+)/H(+) exchanger 7 (NHE7)-knockdown and -overexpressing cells. The properties of cells were studied using functional assays. pH biosensor was used to evaluate the intracellular and endosomal pH. The expression of NHE7 in patients' liver tissues was examined by immunofluorescent staining. Inducible silencing of NHE7 in establCancer communications (London, England)NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma.PMC10876205HMUMIF-220082021111590092020-036HN2023‐02LH2023H043XJ202001217105322HN2023-022020‐036Ma HTYu LYao YFung HLYun JPXue TMYam JWPXiao ZJTin PCXu YfalseNHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma.<h4>Background</h4>Small extracellular vesicles (sEVs) mediate intercellular communication that contributes to hepatocellular carcinoma (HCC) progression via multifaceted pathways. The success of cell entry determines the effect of sEV on recipient cells. Here, we aimed to delineate the mechanisms underlying the uptake of sEV in HCC.<h4>Methods</h4>Macropinocytosis was examined by the ability of cells to internalize dextran and sEV. Macropinocytosis was analyzed in Na(+)/H(+) exchanger 7 (NHE7)-knockdown and -overexpressing cells. The properties of cells were studied using functional assays. pH biosensor was used to evaluate the intracellular and endosomal pH. The expression of NHE7 in patients' liver tissues was examined by immunofluorescent staining. Inducible silencing of NHE7 in establ2024-01-01T00:00:00Z2024 Feb2026-07-15T09:54:58.439Z2026-07-03T03:10:17.144ZS-EPMC108762053815299210.1002/cac2.12515