N-myristoyltransferase: A potential novel diagnostic marker for colon cancer

Shrivastav, Anuraag; Varma, Shailly; Saxena, Anurag; DeCoteau, John F.; Sharma, Rajendra K.

doi:10.1186/1479-5876-5-58

Cited by 22 publications

(21 citation statements)

References 9 publications

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“…Further research will be necessary to determine the specific targets of tris DBA at cilia as well as the signaling mechanisms that regulate cilia-dependent directed migration in pancreatic cancer cells. Several studies suggest that NMT1 activity is important for the progression of different malignancies including breast cancer [31], oral squamous cell carcinoma [32], colon carcinoma [33] and gallblader cancer [34]. Our findings suggest that NMT1 is a novel therapeutic target in pancreatic cancer and warrants further investigation of tris DBA as a potential novel treatment for pancreatic carcinoma.…”

Section: Discussionmentioning

confidence: 57%

Tris DBA palladium is highly effective against growth and metastasis of pancreatic cancer in an orthotopic model

et al. 2016

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Pancreatic carcinoma ranks among the most lethal of human cancers. Besides late detection, other factors contribute to its lethality, including a high degree of chemoresistance, invasion, and distant metastases. Currently, the mainstay of therapy involves resection of local disease in a minority of patients (Whipple procedure) and systemic gemcitabine. While systemic chemotherapy has some benefit, even with optimal treatment, the five year survival after diagnosis is dismal. Thus, treatment of pancreatic carcinoma remains a tremendous unmet need.The organometallic compound tris DBA palladium is a potent inhibitor of N-myristoyltransferase 1 (NMT1), an enzyme that catalyzes the transfer of myristate to protein substrates. This compound is highly effective in vivo against murine models of melanoma with both mutant and wild type b-RAF genotypes. Based upon the signaling similarities between melanoma and pancreatic carcinoma, we evaluated the efficacy of tris DBA palladium in vitro and in vivo against pancreatic carcinoma. We found that tris DBA palladium decreased proliferation and colony formation of pancreatic cancer cells in vitro. In an orthotopic mouse model, tris DBA palladium was highly active in inhibiting growth, ascites production, and distant metastases in vivo. Furthermore, tris DBA palladium impaired chemotaxis and inhibited cilia formation in Pan02 cells in a NMT1-dependent manner. We propose that NMT1 is a novel regulator of cilia formation and tris DBA palladium a novel inhibitor of cilia formation and metastasis in pancreatic cancer. Thus, further evaluation of tris DBA palladium for the treatment of pancreatic cancer is warranted.

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Section: Discussionmentioning

confidence: 57%

Tris DBA palladium is highly effective against growth and metastasis of pancreatic cancer in an orthotopic model

et al. 2016

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“…Isolated peripheral blood mononuclear cells from peripheral blood of control or tumorbearing rats were assessed for NMT activity by using cAMP-dependent protein-kinasederived peptide substrate. Inset Western blot analysis of protein extracts from PBMC and BMC of control and colorectal tumor-bearing rats [adapted from Shrivastav et al 2007] …”

Section: Discussionmentioning

confidence: 99%

N-myristoyltransferase in the leukocytic development processes

et al. 2011

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The lipidic modification of proteins has recently been shown to be of immense importance, although many of the roles of these modifications remain as yet unidentified. One of such key modifications occurring on several proteins is the covalent addition of a 14-carbon long saturated fatty acid, a process termed myristoylation. Myristoylation can occur during both co-translational protein synthesis and posttranslationally, confers lipophilicity to protein molecules, and controls protein functions. The protein myristoylation process is catalyzed by the enzyme Nmyristoyltransferase (NMT), which exists as two isoforms: NMT1 and NMT2. NMT1 is essential for growth and development, during which rapid cellular proliferation is required, in a variety of organisms. NMT1 is also reported to be elevated in many cancerous states, which also involve rapid cellular growth, albeit in an unwanted and uncontrolled manner. The delineation of myristoylation-dependent cellular functions is still in a state of infancy, and many of the roles of the myristoylated proteins remain to be established. The development of cells of the leukocytic lineage represents a phase of rapid growth and development, and we have observed that NMT1 plays a role in this process. The current review outlines the roles of NMT1 in the growth and differentiation of the cells of leukocytic origin. The described studies clearly demonstrate the roles of NMT1 in the regulation of the developmental processes of the leukocytes cells and provide a basis for further research with the aim of unraveling the roles of protein myristoylation in both cellular and physiological context.

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“…It is now apparent that NMT represents both a valuable clinical marker and therapeutic target for cancer (Boutin, 1997;Ducker et al, 2005;Selvakumar et al, 2007;Wright et al, 2009). A several fold increase in NMT activity in polyps and stage B1 tumors compared to normal colonic mucosa have been proposed to be used as a diagnostic/prognostic tool for early detection of colorectal cancer (Raju et al, 1997;Shrivastav et al, 2007;Kumar et al, 2011).…”

Section: Various Cancersmentioning

confidence: 99%

“…However, due to the lack of early symptoms, the majority of the patients have an advanced disease at presentation (Midgley et al, 2001;Segal and Saltz, 2009). Studies have shown that NMT represents both a valuable marker for clinical diagnosis and as a therapeutic target for colon cancer (Magnuson et al, 1995;Raju et al, 1997;Shrivastav et al, 2007;Kumar et al, 2011). Prognosis A direct relationship has been reported for NMT expression and activity and colon cancer progression (Magnuson et al, 1995;Raju et al, 1997).…”

Section: Diseasementioning

confidence: 99%