1. B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2
- Author
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Youquan Bu, Tao Liu, Xiaoyan Fan, Chunxue Zhang, Yunlong Lei, Yuelei Jin, Zhongyu Liu, Yitao Wang, Yulong Niu, Kailong Du, and Tinghui Jiang
- Subjects
0301 basic medicine ,Transcriptional Activation ,Cancer Research ,animal structures ,Colorectal cancer ,Cell Cycle Proteins ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,Transactivation ,0302 clinical medicine ,Genetics ,medicine ,Humans ,RNA, Messenger ,Molecular Biology ,Protein kinase B ,Transcription factor ,Cancer genetics ,E2F2 ,Regulation of gene expression ,fungi ,medicine.disease ,030104 developmental biology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Cancer research ,Trans-Activators ,Signal transduction ,Carcinogenesis ,Cell Division ,Transcription Factors - Abstract
B-Myb is an important transcription factor that plays a critical role in gene expression regulation and tumorigenesis. However, its functional implication in colorectal cancer remains elusive. In this study, we found that B-Myb was significantly upregulated at both mRNA and protein levels in colorectal cancer samples compared to non-tumor counterparts. B-Myb overexpression accelerated cell proliferation, cell cycle progression and cell motility in colorectal cancer cells, and promoted tumor growth in orthotopic nude mouse models in vivo. In contrast, B-Myb depletion inhibited these malignant phenotypes. Mechanistic investigations revealed that E2F2 was a novel transcriptional target of B-Myb and is essential to B-Myb-induced malignant phenotypes. Notably, B-Myb and E2F2 exhibited positive expression correlation, and interacted with each other in colorectal cancer cells. In addition to their autoregulatory mechanisms, B-Myb and E2F2 can also directly transactivate each other, thus constituting consolidated reciprocal feed-forward transactivation loops. Moreover, both B-Myb and E2F2 are required for the activation of ERK and AKT signaling pathways in colorectal cancer cells. Taken together, our data clarified a critical role for B-Myb in colorectal cancer and unraveled an exquisite mutual collaboration and reciprocal cross regulation between B-Myb and E2F2 that contribute to the malignant progression of human colorectal cancer.
- Published
- 2021