ArticleCancer communications (London, England)2024
NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma.
Article in Cancer communications (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- NHE7-Driven endoplasmic reticulum stress signaling transmission promotes malignant progression of endometrial cancer via c-Fos/PRSS1/ERP27 axis.Journal of experimental & clinical cancer research : CR · 2026Article
- CD147-positive migrasome macropinocytosis promotes HCC sorafenib resistance via inducing vasculogenic mimicry triggered by PI3K/AKT/TWIST1 signaling.Cell death & disease · 2026Article
- Hypoxic glycolysis-driven histone lactylation activates NHE7 to promote endometrial cancer progression via COX6C-mediated endoplasmic reticulum stress.Apoptosis : an international journal on programmed cell death · 2026Article
- Exosome-Mediated Regulation of Aerobic Glycolysis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications.Journal of hepatocellular carcinoma · 2026Review
- Lysophosphatidic acid-induced Arf6-driven macropinocytosis of CD147International journal of biological sciences · 2026Article
- Acidic Tumor Microenvironments and Emerging Therapeutic Strategies for Cancer Therapy.Yonsei medical journal · 2025Review
- K-562 Extracellular Vesicles Partially Protect Intact Cells from Oxidative Stress and Provide Limited Resistance to Imatinib.Current issues in molecular biology · 2025Article
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma.Cancer communications (London, England) · 2024Article
- Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSmall 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.
methodsMacropinocytosis 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 established tumors was performed to reveal the therapeutic potential of targeting NHE7.
resultsThe data revealed that macropinocytosis controlled the internalization of sEVs and their oncogenic effect on recipient cells. It was found that metastatic HCC cells exhibited the highest efficiency of sEV uptake relative to normal liver cells and non-metastatic HCC cells. Attenuation of macropinocytic activity by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) limited the entry of sEVs and compromised cell aggressiveness. Mechanistically, we delineated that high level of NHE7, a sodium-hydrogen exchanger, alkalized intracellular pH and acidized endosomal pH, leading to the maturation of macropinosomes. Inducible inhibition of NHE7 in established tumors developed in mice delayed tumor development and suppressed lung metastasis. Clinically, NHE7 expression was upregulated and linked to dismal prognosis of HCC.
conclusionsThis study advances the understanding that NHE7 enhances sEV uptake by macropinocytosis to promote the malignant properties of HCC cells. Inhibition of sEV uptake via macropinocytosis can be exploited as a treatment alone or in combination with conventional therapeutic approaches for HCC.
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