Biochemical and Biophysical Research Communications
Regular ArticleHypoxia Induces the Expression of a 43-kDa Protein (PROXY-1) in Normal and Malignant Cells
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Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy
2014, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :Multiple other agents, including Ca2 + [139] and heavy metal ions (e.g., Co2 + [140], Ni2 + [42,140]), androgens [68,125], DNA-damaging agents (e.g., actinomycin D), forskolin [65], lysophosphatidylcholine [30], okadaic acid [42,141], sulfhydryl reducing agents and tunicamycin [40], ligands of the peroxisome proliferator-activated receptor (PPAR)-γ and retinoid X receptor (RXR) [25], iron chelators [96,111,142,143] and vitamins A and D3 [70,144,145] also promote NDRG1 expression [49,146]. Further, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) [23,43,147], p53 [41,79,148–150] and the von Hippel–Lindau protein (pVHL) [32] have been reported to promote NDRG1 expression. Three hypoxia-inducible factor (HIF)-1-binding sites have been identified in the non-coding sequence of NDRG1, of which one is located in the promoter region and two are located in the 3′ untranslated region [151].
NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer
2012, Journal of Thoracic OncologyMetastasis suppressor genes. At the interface between the environment and tumor cell growth
2011, International Review of Cell and Molecular BiologyCitation Excerpt :Drg1 was first identified as a tumor suppressor in human bladder and pancreatic cancers (Kurdistani et al., 1998), but overexpression in breast, colon, and prostate cancer cell lines suppressed metastasis without suppressing tumorigenicity (Guan et al., 2000), a pattern which is supported in limited clinical studies in breast, prostate, and liver cancers (Bandyopadhyay et al., 2003; Chua et al., 2007). DRG-1 appears to be downstream of many cancer- and metastasis-associated signaling pathways, such as p53 (Kim et al., 2004; Kurdistani et al., 1998), PI3K/PTEN (Bandyopadhyay et al., 2004), PKC (Fujii et al., 2008), hypoxia (Agarwala et al., 2000; Bandyopadhyay et al., 2003; Park et al., 2000), and in breast and prostate tumors, estrogens and androgens (Ulrix et al., 1999). Downstream mediators include VEGF and IL8 which are both involved in angiogenesis (Maruyama et al., 2006).
NDRG1/2 expression is inhibited in primary acute myeloid leukemia
2010, Leukemia ResearchCitation Excerpt :Further studies are needed to clarify whether NDRG1 directly or indirectly enhances expression of myeloid transcription factors. Moreover, NDRG1 is upregulated under hypoxic conditions [21], and low oxygen conditions were shown to promote maturation of myeloid leukemic cells (reviewed in [22]). In addition, ATRA-induced HIF-1α protein might not only enhance neutrophil differentiation by increasing the transcriptional activity of the myeloid-associated transcription factors C/EBPA and AML1 [23], but also by inducing NDRG1 via HIF-1α.
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