AKT1 phosphorylates RBM17 to promote Sox2 transcription by modulating alternative splicing of FOXM1 to enhance cancer stem cell properties in colorectal cancer cells. Issue 1 (15th December 2022)

• Record Type: Journal Article
• Authors: Fu, Yan; Bai, Chen; Wang, Shengsheng; Chen, Denggang; Zhang, Peng; Wei, Hailang; Rong, Fan; Zhang, Chao; Chen, Shaojuan; Wang, Zhenjun
• Is Part Of: FASEB journal. Volume 37:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-15
• Subjects: alternative splicing -- cancer stem cells -- colorectal cancer -- RBM17; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202201255R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. The existence of cancer stem cells (CSC) causes tumor relapses, metastasis, and resistance to conventional therapy. Alternative splicing has been shown to affect physiological and pathological processes. Accumulating evidence has confirmed that targeting alternative splicing could be an effective strategy to treat CRC. Currently, the role of alternative splicing in the regulation of CSC properties in CRC has not been elucidated. Here, we show that RBM17 displays oncogenic roles in CRC cells. RBM17 enhances cell proliferation and reduces chemotherapeutic‐induced apoptosis in CRC cells. Besides, RBM17 increases CD133 positive and ALDEFLUOR positive populations and promotes sphere formation in CRC cells. In mechanism studies, we found that FOXM1 is critical for RBM17 enhanced CSC properties. Moreover, FOXM1 alternative splicing is essential for RBM17 enhanced CSC properties in CRC cells. Additionally, RBM17 enhances CSC characteristics by controlling FOXM1 expression to promote Sox2 expression. Furthermore, AKT1 works as an upstream kinase to control RBM17‐mediated FOXM1 alternative splicing and enhancement of CSC properties in CRC cells. Our study reveals that AKT1‐RBM17‐FOXM1‐Sox2 axis could be a potential target for modulating alternative splicing to reduce CSC properties in CRC cells.