Knockdown of NDRG1 promote epithelial-mesenchymal transition of colorectal cancer via NF-κB signaling

Abstract

NDRG1 appears to prevent EMT-induced metastasis by attenuating NF-κB signaling in mCRC. NDRG1 may be an independent prognostic factor for good survival of mCRC. J. Surg. Oncol. 2016;114:520-527. © 2016 Wiley Periodicals, Inc.

Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets

“…This gene which has a mixed expression trend in MvsP analysis is one of the repressors of the EMT in metastatic CRC by attenuating NF-κB signaling [97]. Inhibition of NDRG1 results in the increase in NF-kB and the reduction in E-cadherin [98]. The promoter region of the NDRG1 gene contains a p53 binding site which is necessary in caspase activation and apoptosis in the case of DNA damage [99].…”

A combined literature and in silico analysis enlightens the role of the NDRG family in the gut

“…When looking at separate stages, the survival rate of stage II and IV patients with preserved NDRG1 mRNA expression in the tumor was significantly better compared to patients with reduced NDRG1 tumor levels (P=0.0005) [40]. In addition, the disease free survival (DFS) and progression free survival (PFS) rate were 1.3-2.0 fold higher for the patients with preserved NDRG1 protein expression in the tumor compared to the ones having reduced NDRG1 tumor levels (P=0.003-0.004) [42,54], suggesting that NDRG1 is an independent prognostic factor for both recurrence and overall survival. Interestingly, Koshiji et al reported that NDRG1 expression significantly correlated with Duke's stage in Japanese (P=0.036), and Caucasians (P=0.0063), but not in African Americans (P=0.880).…”

“…Moreover, these studies found NDRG1 to be an independent, favorable prognostic factor for CRC. In fact, when not differentiating between cancer stages, the overall survival (OS) rate for CRC patients with NDRG1 expression was remarkably higher compared to those with reduced NDRG1 levels (P=0.000-0.148) [40,42,43,54]. When looking at separate stages, the survival rate of stage II and IV patients with preserved NDRG1 mRNA expression in the tumor was significantly better compared to patients with reduced NDRG1 tumor levels (P=0.0005) [40].…”

“…by N-acetyl-L-cysteine) of primary colon cancer cell lines (e.g. HT29) (23,26,55,60), and (iv) the induction of morphological changes and increased expression of important epithelial cell differentiation markers by NDRG1 overexpression in metastatic colon cancer cells [23,54].…”

“…Only a very limited number of studies have investigated the predictive value of NDRG1 in CRC cell lines and CRC patients [43,54] Irinotecan-based therapy, as patients who developed a recurrence while having high NDRG1 tumor levels, received Irinotecan-based therapy only for 6.8 months, whereas those with a low tumor level of NDRG1 remained on this therapy for 9.3 months (P=0.070) [43]. No studies have explored the predictive biomarker value for either NDRG2, 3 or 4.…”