Abstract
Colon cancer is one of the most common malignant diseases and a major cause of mortality in the Western world. Metastasis to lymph nodes and other gastrointestinal organs, especially to the liver and lungs, is most common and occurs in up to 25% of cancer patients when initially diagnosed. The majority of colon cancers develop from noncancerous adenomatous polyps on the lining of the colon which grow over the years to become cancerous. If detected early, the surgical resections of the growth, often in combination with chemotherapy, significantly increases life expectancy. We have shown that the enzyme N-myristoyltransferase (NMT) which carries out lipid modification of several proteins (including many of those involved in oncogenesis) is expressed at higher levels in cancerous tissues from the colon. We have also shown that in peripheral blood mononuclear cells (PBMC) and bone marrow (BM) cells collected from colon cancer patients and from azoxymethane-induced rats the expression and localization of NMT is altered. We have observed strong positivity for NMT in immunohistochemical analysis for PBMC from colon cancer patients as compared to control groups. Furthermore, in the bone marrow (BM) mononuclear cells, NMT was found to be confined to the nuclei whereas in control groups it was observed to be located in the cytoplasm. In conclusion, this strikingly differential localization offers the basis of a potential investigational tool for screening or diagnosis of individuals at risk for or suspected of having colon cancer.
Highlights
Colorectal cancer is one of the most common forms of malignancy worldwide and is associated with high mortality [1]
More than 50% of the cells appeared to be positive in immunohistochemical analysis with anti-peptide antibody in all eight cases of human adenocarcinoma tissue samples studied (Figure 2a)
NMT activity in tumor bearing rats was three-fold higher in peripheral blood mononuclear cells (PBMC) whereas it was elevated by five-fold in bone marrow (BM) cells as compared to control group (Figure 3a)
Summary
Colorectal cancer is one of the most common forms of malignancy worldwide and is associated with high mortality [1]. Lipidic modification of proteins has received great attention recently as targets for therapeutic interventions to cancer [7,8,9,10] One such candidate is the N-myristoylation process catalyzed by the enzyme N-myristoyltransferase [9,10]. A differential expression of pp60c-src has been observed in colonic tumor-derived cell lines [19,21] and colonic polyps prone to developing cancer [24]. It has been observed that in colon cancer cell lines elevated expression of NMT correlates with high levels of c-Src levels [25]. Studies have revealed that pp60c-src is overexpressed in human colon carcinoma and it has enhanced kinase activity in progressive stages and metastases of human colorectal cancer [19,20]. The current review summarizes the developments in using NMT as a suitable sensitive and specific biomarker which merits further investigation to perform a risk assessment for the early stages of colorectal neoplasia
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