Myristoyl-CoA:protein N-myristoyltransferase: a novel molecular approach for cancer therapy (Review).
Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. The treatment of colonic cancer remains difficult because of the lack of effective chemotherapeutic agents; therefore it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs resulting in the inhibition of the development and progression of cancer. The current knowledge of the modification of proteins by myristoylation involving myristoyl-CoA:protein N-myristoyltransferase (NMT) is in its infancy. This process is involved in the pathogenesis of cancer. We have reported for the first time in rats treated with azoxymethane that NMT activity was higher in colonic epithelial neoplasms than in normal colonic tissue and that an increase in NMT activity appeared at an early stage in colonic carcinogenesis. Increased NMT activity was also confirmed in human colonic tumors compared to normal tissue. Furthermore, colorectal tumors displayed increased immunohistochemical staining for NMT compared to normal mucosa in the cytoplasm. In addition, gallbladder carcinoma showed moderate to strong cytoplasmic positivity for NMT with increased intensity in the invasive component whereas the normal gallbladder mucosa showed weak to negative cytoplasmic staining for this enzyme. It is conceivable therefore that NMT can be used as a potential marker for the early detection of cancer. Of particular note is the very recent discovery of cytotoxic compounds in the laboratories of the authors which inhibit NMT and may offer a novel approach for the evolution of candidate antineoplastic agents which display greater potencies towards neoplasms than the corresponding normal tissues.
Selvakumar
Ponniah
P
Department of Pathology and Cancer Research Unit, College of Medicine and Saskatchewan Cancer Agency, Saskatoon, SK, Canada.
Pasha
Mohammed Khysar
MK
Ashakumary
Lakshmikuttyamma
L
Dimmock
Jonathan R
JR
Sharma
Rajendra K
RK
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002277:Carcinoma / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000378:metabolism; D006801:Humans; D051381:Rats
D015415:Biomarkers; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase