Inhibitory effect of upregulated DR-nm23 expression on invasion and metastasis in colorectal cancer

Abstract

To explore the role of DR-nm23 in the regulation of colorectal cancer invasion and metastasis. Immunohistochemistry assay and in-situ nucleic acid hybridization were carried out to analyze the protein and mRNA expression of DR-nm23 in patient samples. The molecular cloning technique was applied to construct the recombinant lentiviral expression vector pGC-FU-DR-nm23-GFP. Lentiviral infection was used to introduce overexpression of exogenous DR-nm23 in SW620 colorectal cancer cells. Both in-vitro cell experiments and an in-vivo xenograft tumor model assay were carried out to determine the role of DR-nm23 in the regulation of colorectal cancer proliferation, invasion, and metastasis. Our data here showed that the expression level of DR-nm23 in colorectal cancer tissue was significantly lower than that in adenoma and normal tissue. The expression level of DR-nm23 was also found to be negatively correlated with lymph node metastasis and positively correlated with the degree of tumor differentiation. Besides, introduced overexpression of DR-nm23 in SW620 cells through lentiviral infection resulted in significant inhibition of its proliferation rate in vitro and growth rate in vivo. The cell migration ability in vitro and metastatic potential in vivo were also impaired at the same time. Our current study suggested that DR-nm23 may participate in the regulation of differentiation of colorectal cancer cells. Its downregulated expression is closely related to the invasion and metastasis of colorectal cancer. Thus, expression status of DR-nm23 may act as a potential prognostic factor in patients with colorectal cancer.

Mutation of the nm23-H1 gene has a non-dominant role in colorectal adenocarcinoma

“…The expression of DR-nm23 in colorectal cancer tissue was significantly lower compared with that in adenoma and normal tissue. Therefore, the expression status of DR-nm23 may act as a potential prognostic factor in patients with colorectal cancer, and it may be involved in the regulation of differentiation of colorectal cancer cells (12). At the invasive front of colon carcinoma, nm23-H1 levels were also reduced or lost, and its downregulated expression was closely associated with the invasion and metastasis of colorectal cancer (13).…”

Correlation between non-metastatic protein 23 expression and clinicopathological features of colorectal cancer in Asians

“…Qualitative analysis was performed on 21 studies selected. Finally, 16 studies published from 1999-2014 were incorporated into our meta-analysis (Feng et al, 1999;He et al, 2000;Yu et al, 2000;Liu and Wang, 2001;Wang et al, 2001;Zhen et al, 2002;Zhang et al, 2003;Su and Li, 2004;Liu et al, 2005;Ba, 2006;Gao, 2006;Chen et al, 2007;Song et al, 2010;Wu et al, 2013;Qu et al, 2013;Cui et al, 2014). The baseline characteristics and NOS scores of the 16 eligible studies are summarized in Table 1 …”

“…The exact mechanism for the origin and development of CRC remains unclear. Previous studies have shown that inactivation of NM23 plays an important role in the development of CRC (Wu et al, 2013;Qu et al, 2013). We explored the correlation between NM23 expression, tumor pathology, and tumor prognosis to better understand the influence of NM23 status on CRC progression and survival.…”

“…©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 15597-15608 (2015) motility, expression of protein hydrolases, and formation of new blood vessels (Tan et al, 2012;Qu et al, 2013). NM23-H1 was the first identified metastasis suppressor gene and belongs to a group of 8 closely related genes, Nm23H1-H8.…”

Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified

“…Upon developing chemically induced liver cancer, Nme1-deficient mice formed significantly greater lung metastases than wild-type mice (Boissan et al 2005), confirming a metastasis suppressor activity. Recent articles have expanded the breadth of metastasis suppression to Nme1 in UV radiation-induced melanoma (Jarrett et al 2013) and lung cancer (Fan et al 2013) and to Nme3 (also named Nm23-DR) in colorectal cancer (Qu et al 2013). The function of Nme1 has also expanded to some aspects of tumorigenesis (Jarrett et al 2011).…”