Identification of High-Risk Stage II Colorectal Tumors by Combined Analysis of the NDRG1 Gene Expression and the Depth of Tumor Invasion

Strzelczyk, Barbara; Szulc, Aneta; Rzepko, Robert; Kitowska, Agnieszka; Skokowski, Jarosław; Szutowicz, Andrzej; Pawełczyk, Tadeusz

doi:10.1245/s10434-009-0381-0

Cited by 52 publications

(51 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, NDRG1 was found to be negatively correlated with tumor progression, while being positively correlated with better patient prognosis for a range of cancers, including those of the prostate, breast, colon, and pancreas (5,(11)(12)(13)16). Considering the potential therapeutic implications of utilizing NDRG1 as a molecular target for the treatment of cancer, the molecular mechanisms by which NDRG1 is able to exert its anti-cancer effects have recently become the subject of intense research.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, studies examining the prognosis of patients with these latter neoplasms demonstrated that those with higher NDRG1 levels had a significantly better outcome when compared with those with low NDRG1 levels (5,(11)(12)(13). Hence, NDRG1 is a promising prognostic indicator and molecular target for these cancers (14), which represent some of the most common and fatal neoplastic conditions.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

Kovačević

Menezes

Sahni

et al. 2016

Journal of Biological Chemistry

113

View full text Add to dashboard Cite

N-MYC downstream-regulated gene-1 (NDRG1) is a potent growth and metastasis suppressor that acts through its inhibitory effects on a wide variety of cellular signaling pathways, including the TGF-␤ pathway, protein kinase B (AKT)/PI3K pathway, RAS, etc. To investigate the hypothesis that its multiple effects could be regulated by a common upstream effector, the role of NDRG1 on the epidermal growth factor receptor (EGFR) and other members of the ErbB family, namely human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3), was examined. We demonstrate that NDRG1 markedly decreased the expression and activation of EGFR, HER2, and HER3 in response to the epidermal growth factor (EGF) ligand, while also inhibiting formation of the EGFR/HER2 and HER2/HER3 heterodimers. In addition, NDRG1 also decreased activation of the downstream MAPKK in response to EGF. Moreover, novel anti-tumor agents of the di-2-pyridylketone class of thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, which markedly up-regulate NDRG1, were found to inhibit EGFR, HER2, and HER3 expression and phosphorylation in cancer cells. However, the mechanism involved appeared dependent on NDRG1 for di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, but was independent of this metastasis suppressor for di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone. This observation demonstrates that small structural changes in thiosemicarbazones result in marked alterations in molecular targeting. Collectively, these results reveal a mechanism for the extensive downstream effects on cellular signaling attributed to NDRG1. Furthermore, this study identifies a novel approach for the treatment of tumors resistant to traditional EGFR inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

Kovačević

Menezes

Sahni

et al. 2016

Journal of Biological Chemistry

113

View full text Add to dashboard Cite

show abstract

“…N-Myc downstream-regulated gene 1 (NDRG1), also named differentiation-related gene-1, is involved in the development of central nervous system (33). NDRG1 was reported as a differentiation marker of breast cancer (34) and prognosticates better survival in CRCs (35). The IFG1R was considered as another differentiation-related gene in lung adenocarcinoma (29).…”

Section: Discussionmentioning

confidence: 99%

Secreted Protein Acidic and Rich in Cysteines-like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers

Zhang

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is an extracellular matrix glycoprotein with malignancy-suppressing potential. The hypothesis that SPARCL1 reduces cancer invasiveness and predicts better survival in colorectal cancers (CRC) was investigated.Experimental Design: Stable SPARCL1 transfectants, RKO-SPARCL1, and corresponding vector control were constructed and implanted into nude mice to generate a mouse xenograft model of liver metastasis. Also, a retrospective outcome study was conducted on the COH set (222 CRCs) and ZJU set (412 CRCs). The protein expression level of SPARCL1 was determined by immunohistochemistry. The Kaplan-Meier and Cox analyses were used for survival analysis. The association of SPARCL1 with mesenchymal-epithelial transition (MET) was examined by reverse transcription PCR (RT-PCR) and Western blot analysis.Results: The ectopic expression of SPARCL1 significantly reduced the potential for anchorage-independent growth, migration, invasion and induced cell differentiation in RKO and SW620 cells. In mouse xenograft model, the expression of SPARCL1 significantly reduced the liver metastasis (P < 0.01). The patient-based studies revealed that the expression of SPARCL1 was related to better differentiation (P < 0.01), less lymph node involvement [OR, 0.67; 95% confidence interval (CI), 0.45-1.00], and less distant metastasis (OR, 0.38; 95% CI, 0.18-0.79). The Kaplan-Meier and Cox analysis showed that the expression of SPARCL1 was associated with better overall survival (log-rank: P < 0.01; HR, 0.57; 95% CI, 0.39-0.84). Transfection of SPARCL1 induced MET of colon cancer cells.Conclusion: SPARCL1 functions as a tumor suppressor promoting differentiation possibly via MET, which inhibits the aggressiveness of CRCs.

show abstract

“…However, these studies have revealed controversial results for the manner of NDRG1 regulation by HIF-1α under hypoxia. Various of these studies reported a marked upregulation of the NDRG1 expression level under hypoxic conditions, whereas others have shown downregulated NDRG1 under the same conditions (8,(13)(14)(15)18,19,25). Consequently, the regulation of NDRG1 under hypoxia is highly complex and its cellular function is still a matter of debate.…”

Section: Time-and Oxygen-dependent Expression and Regulation Of Ndrg1mentioning

confidence: 99%

“…with unfavorable patient prognosis in glioma (13), colorectal cancer (14), esophageal squamous cell carcinoma (15), pancreatic ductal adenocarcinoma (16), prostate (17,18) and breast cancer (19).…”

Section: Time-and Oxygen-dependent Expression and Regulation Of Ndrg1mentioning

confidence: 99%

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

et al. 2017

View full text Add to dashboard Cite

Abstract. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the regulation of NDRG1 to the transcription factors HIF-1α, SP1, CEBPα, YB-1 and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87-MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O 2 ) conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF-1α SP1, CEBPα, YB-1 and Smad7 was measured using semi-quantitative RT-PCR analysis. Their protein expression was analyzed using western blotting. Our experiments revealed that long-term (24 h), but not short-term hypoxia led to the induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was found to correlate with the protein expression of HIF-1α, SP1, CEBPα, YB-1 and Smad7. The present study suggests for the first time that SP1 regulates NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along with HIF-1α, CEBPα, YB-1 and Smad7. These molecules, each separately or in combination, may possess the potential to become target molecules for antitumor therapeutic approaches particularly in human brain tumors.

show abstract

Identification of High-Risk Stage II Colorectal Tumors by Combined Analysis of the NDRG1 Gene Expression and the Depth of Tumor Invasion

Cited by 52 publications

References 23 publications

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways

Secreted Protein Acidic and Rich in Cysteines-like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

Contact Info

Product

Resources

About