Bidirectional regulation between NDRG1 and GSK3b controls tumor growth and is targeted by differentiation inducing factor-1 in glioblastoma. Ito H, Watari K, Shibata T, Miyamoto T, Murakami Y, Nakahara Y, et al. NDRG1 in aggressive breast cancer progression and brain metastasis. Villodre ES, Hu X, Eckhardt BL, Larson R, Huo L, Yoon EC, et al. NDRG1 regulates neutral lipid metabolism in breast cancer cells. Sevinsky CJ, Khan F, Kokabee L, Darehshouri A, Maddipati KR, Conklin DS. The metastasis suppressor, NDRG1, differentially modulates the endoplasmic reticulum stress response. Merlot AM, Porter GM, Sahni S, Lim EG, Peres P, Richardson DR. N-myc downstream regulated 1 (NDRG1) is regulated by eukaryotic initiation factor 3a (eIF3a) during cellular stress caused by iron depletion. Lane DJ, Saletta F, Suryo Rahmanto Y, Kovacevic Z, Richardson DR. Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter. The role of NDRG1 in the pathology and potential treatment of human cancers. 2015 63:1164–72.īae DH, Jansson PJ, Huang ML, Kovacevic Z, Kalinowski D, Lee CS, et al. Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma. Nio K, Yamashita T, Okada H, Kondo M, Hayashi T, Hara Y, et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Münz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. EpCAM‑regulated intramembrane proteolysis induces a cancer stem cell‑like gene signature in hepatitis B virus‑infected hepatocytes. Mani SK, Zhang H, Diab A, Pascuzzi PE, Lefrançois L, Fares N, et al. CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line. 2012 55:807–20.Īsai R, Tsuchiya H, Amisaki M, Makimoto K, Takenaga A, Sakabe T, et al. CD133(+) liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling. Tang KH, Ma S, Lee TK, Chan YP, Kwan PS, Tong CM, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, et al. USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation. Ling S, Shan Q, Zhan Q, Ye Q, Liu P, Xu S, et al. Cancer stem cells in the development of liver cancer. Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma. Zheng H, Pomyen Y, Hernandez MO, Li C, Livak F, Tang W, et al. Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients. TGF-β-miR-34a-CCL22 signaling-induced treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ, Ning S, et al. FSTL1 secreted by activated fibroblasts promotes hepatocellular carcinoma metastasis and stemness. Loh JJ, Li TW, Zhou L, Wong TL, Liu X, Ma VW, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. NDRG1 may be a promising target for the treatment of patients with HCC and PVTT.īray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Our findings suggest that NDRG1 enhances CSCs expansion, PVTT formation and growth capability through the regulation of EpCAM stability. NDRG1 was found to stabilise the functional tumour-initiating cell marker EpCAM through protein–protein interactions and inhibition of EpCAM ubiquitination. In addition, NDRG1 knockdown inhibited the proliferation and migration of PVTT-1 cells in vitro and in vivo. Our functional study showed that NDRG1 was required for the self-renewal of tumour-initiating/cancer stem cells (CSCs). Furthermore, NDRG1 expression was enhanced in the PVTT samples. NDRG1 protein was upregulated in HCC samples compared to non-tumorous tissues. The relationship between NDRG1 and EpCAM was explored using molecular biological techniques. The functional relevance of NDRG1 was evaluated using sphere formation and animal models of tumorigenicity and metastasis. NDRG1 expression was assessed by immunohistochemistry and immunoblotting in clinical specimens obtained from curative surgery. However, the molecular mechanisms underlying PVTT vascular metastases have not been fully elucidated. Portal vein tumour thrombus (PVTT) is the main pathway of HCC intrahepatic metastasis and is responsible for the poor prognosis of patients with HCC.
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