Ebp1 p48 promotes oncogenic activities in human colon cancer cells through regulation of TIF‐90‐mediated ribosomal RNA synthesis. Issue 10 (22nd February 2019)

• Record Type: Journal Article
• Authors: Nguyen, Dang Quan; Hoang, Dinh Hoa; Nguyen, Thanh Thao Vo; Ho, Huu Duc; Huynh, Vu; Shin, June Ho; Ly, Quoc Trung; Thi Nguyen, Dai Dong; Ghoda, Lucy; Marcucci, Guido; Nguyen, Le Xuan Truong
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 10(2019:Oct.)
• Page Start: 17612
• Page End: 17621
• Publication Date: 2019-02-22
• Subjects: colon cancer -- Ebp1 -- rRNA synthesis -- TIF‐90; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28385
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: The ErbB3‐binding protein 1 (Ebp1) has been reported as either an oncogenic regulator or a tumor suppressor in a variety of cancers. Here, we show that Ebp1 p48, a predominant expression isoform, is highly expressed in the majority of human colon tumor cells compared with normal adjacent tissues and its expression is required for the oncogenic activities of these cells. Depletion of Ebp1 expression in primary colon cancer cells inhibits cell proliferation, colony forming, and invasion in vitro as well as tumor formation in vivo and enhances cell sensitivity to irradiation. We further demonstrated that Ebp1 interacts with TIF‐90, a splice variant of transcription initiation factor IA (TIF‐IA) of the RNA polymerase I complex, allowing for regulation of ribosomal RNA (rRNA) synthesis and oncogenesis in human colon cancer cells. Moreover, Ebp1 expression is essential for Akt protected TIF‐90 stability by preventing TIF‐90's ubiquitination by Mdm2 and hence, its proteasomal degradation. The results of the present study support a mechanism of underlying oncogenic activities by means of Ebp1 through regulation of TIF‐90‐mediated rRNA synthesis and suggest the potential therapeutic treatment of colon cancer by targeting Ebp1 and its signaling. Abstract : Ebp1 p48, a predominant expression isoform, is highly expressed in the majority of human colon tumor cells compared with normal adjacent tissues and its expression is required for the oncogenic activities of these cells. Ebp1 interacts with TIF‐90, a splice variant of transcription initiation factor IA (TIF‐IA) of the RNA polymerase I complex allowing for regulation of ribosomal RNA synthesis and oncogenesis in human colon cancer cells.