ArticleCell death & disease2018
Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by regulating tumor associate macrophages polarization.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- The hepatic macrophage: a key regulator of liver metastatic tumor microenvironment through cell crosstalk.Journal of translational medicine · 2025Review
- TRIM26 deficiency potentially suppresses colorectal cancer liver metastasis through NF-κB-mediated M1-like tumor-associated macrophage polarization.British journal of cancer · 2025Article
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Review
- Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.ACS omega · 2024Article
- NF-κB: Governing Macrophages in Cancer.Genes · 2024Review
- Biological Roles and Clinical Therapeutic Applications of Tumor-Associated Macrophages in Colorectal Liver Metastasis.Journal of inflammation research · 2024Review
- Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2023Article
- Role of tumor-associated macrophages in common digestive system malignant tumors.World journal of gastrointestinal oncology · 2023Review
- Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.Translational gastroenterology and hepatology · 2023Review
- Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.Journal of neuroinflammation · 2022Article
- Intracellular and extracellular factors of colorectal cancer liver metastasis: a pivotal perplex to be fully elucidated.Cancer cell international · 2022Review
- M1‑like tumor‑associated macrophages enhance proliferation and anti‑apoptotic ability of liver cancer cells via activating the NF‑κB signaling pathway.Molecular medicine reports · 2022Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Peroxidasin Deficiency Re-programs Macrophages Toward Pro-fibrolysis Function and Promotes Collagen Resolution in Liver.Cellular and molecular gastroenterology and hepatology · 2022Article
- Functional and Therapeutic Significance of Tumor-Associated Macrophages in Colorectal Cancer.Frontiers in oncology · 2022Review
- Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives.Cancers · 2021Review
- The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer.International journal of molecular sciences · 2021Review
- Macrophage Polarization and Liver Ischemia-Reperfusion Injury.International journal of medical sciences · 2021Review
- Macrophage Polarization and Its Role in Liver Disease.Frontiers in immunology · 2021Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion of inhibitory factors, may be a potential therapeutic strategy for liver cancer metastasis treatment.We first cloned NDRG2 (N-myc downstream-regulated gene 2) and verified its tumor suppressor role in multiple solid tumors, including colorectal cancer and hepatocellular carcinoma. However, its role in the tumor-associated liver microenvironment, especially in TAMs, has not been illustrated. By establishing a liver cancer metastasis model in wild-type (WT) and Ndrg2 knockout (Ndrg2-/-) mice, we found that the loss of the tumor suppressor Ndrg2 in liver microenvironment significantly suppressed the growth of liver colonies. In addition, this process was accompanied by a higher proportion of M1-like TAM infiltration in Ndrg2-/- mice. Interestingly, bone marrow (BM) transplantation revealed that BM-derived macrophages (BMDMs) rather than liver resident Kupffer cells were responsible for the inhibitory effect. We further demonstrated that loss of Ndrg2 influenced TAM polarization via the NF-κB pathway. Inhibition of IκBα phosphorylation in cancer cell-conditioned medium-stimulated BMDMs decreased M1 marker expression in Ndrg2-/- macrophages. Finally, in vitro, invasion, migration, and proliferation assays confirmed that NF-κB participated in the tumor suppressor function of Ndrg2-/- macrophages. Collectively, our findings highlight the role of NDRG2 in the regulation of TAM polarization and its function in promoting cancer liver metastasis.
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