c-MYB and DMTF1 in Cancer

Abstract

The c-Myb gene encodes a transcription factor that regulates cell proliferation, differentiation, and apoptosis through protein-protein interaction and transcriptional regulation of signaling pathways. The protein is frequently overexpressed in human leukemias, breast cancers, and other solid tumors suggesting that it is a bona fide oncogene. c-MYB is often overexpressed by translocation in human tumors with t(6;7)(q23;q34) resulting in c-MYB-TCRβ in T cell ALL, t(X;6)(p11;q23) with c-MYB-GATA1 in acute basophilic leukemia, and t(6;9)(q22–23;p23–24) with c-MYB-NF1B in adenoid cystic carcinoma. Antisense oligonucleotides to c-MYB were developed to purge bone marrow cells to eliminate tumor cells in leukemias. Recently small molecules that inhibit c-MYB activity have been developed to disrupt its interaction with p300. The Dmp1 (cyclin D binding myb-like protein 1; Dmtf1) gene was isolated through its virtue for binding to cyclin D2. It is a transcription factor that has a Myb-like repeat for DNA binding. The Dmtf1 protein directly binds to the Arf promoter for transactivation and physically interacts with p53 to activate the p53 pathway. The gene is hemizygously deleted in 35–42% of human cancers, and is associated with longer survival. The significances of aberrant expression of c-MYB and DMTF1 proteins in human cancers and their clinical significances are discussed.

Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature

“…Analysis of tumor specimens showed that MEK1/2 and ERK1/2 phosphorylation was reduced by both drugs alone and completely abrogated only by the combination of the two drugs. The transcription factor c-MYB plays a central role in the development of acute myeloid leukemia (AML) and other tumors [44]. Walf-Vorderwülbecke et al used a c-MYB gene expression signature from AML cells to probe a library containing over 1,500,000 gene expression profiles and identified MBZ as the most efficient c-MYB targeting drug [45].…”

c‐Myb promotes growth and metastasis of colorectal cancer through c‐fos‐induced epithelial‐mesenchymal transition

“…It is reported to be involved in maintaining colonic crypt homeostasis, which is related to its regulatory role in crypt proliferation, integrity and normal differentiation . Although it was originally described to be hematopoietic lineage‐specific, increasing studies have found it is overexpressed in numerous solid tumors and may contribute to the malignant characteristics of cancer cells . For example, c‐Myb is able to drive the invasion and metastasis of breast cancer cells through the Wnt/β‐Catenin/Axin2 signaling pathway .…”

Recent Advances in Oligonucleotide Therapeutics in Oncology

“…G4460 binds to codon sequences 2–9 of the CMYB mRNA and triggers RNAse H dependent degradation [ 89 ]. CMYB is a proto-oncogene that encodes a transcription regulator essential for cell proliferation, differentiation, and apoptosis [ 90 , 91 ]. Over-expression of c-Myb leads to increased proliferation and reduced differentiation in many types of cancers including leukemias and breast cancers [ 91 ].…”

“…CMYB is a proto-oncogene that encodes a transcription regulator essential for cell proliferation, differentiation, and apoptosis [ 90 , 91 ]. Over-expression of c-Myb leads to increased proliferation and reduced differentiation in many types of cancers including leukemias and breast cancers [ 91 ]. A preclinical experiment indicated that the ASO inhibits proliferation of the human leukemia cell line HL-60 by 75%–80% [ 92 , 93 ].…”