Datta Kamal, Suman Shubhankar, Kumar Santosh, Fornace Albert J
1. Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC USA.
1. Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC USA.; 2. Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
J Cancer. 2016 Jan 1;7(2):174-83. doi: 10.7150/jca.13387. eCollection 2016.
Adult colorectal epithelium undergoes continuous renewal and maintains homeostatic balance through regulated cellular proliferation, differentiation, and migration. The canonical Wnt signaling pathway involving the transcriptional co-activator β-catenin is important for colorectal development and normal epithelial maintenance, and deregulated Wnt/β-catenin signaling has been implicated in colorectal carcinogenesis. Colorectal carcinogenesis has been linked to radiation exposure, and radiation has been demonstrated to alter Wnt/β-catenin signaling, as well as the proteasomal pathway involved in the degradation of the signaling components and thus regulation of β-catenin. The current review discusses recent progresses in our understanding of colorectal carcinogenesis in relation to different types of radiation and roles that radiation quality plays in deregulating β-catenin and ubiquitin-proteasome pathway (UPP) for colorectal cancer initiation and progression.
成人结直肠上皮通过调控细胞增殖、分化和迁移进行持续更新并维持稳态平衡。涉及转录共激活因子β-连环蛋白的经典Wnt信号通路对结直肠发育和正常上皮维持至关重要,而Wnt/β-连环蛋白信号失调与结直肠癌发生有关。结直肠癌发生与辐射暴露有关,并且已证明辐射会改变Wnt/β-连环蛋白信号通路以及参与信号成分降解从而调控β-连环蛋白的蛋白酶体途径。本综述讨论了我们在理解不同类型辐射与结直肠癌发生的关系以及辐射质量在结直肠癌起始和进展过程中对β-连环蛋白和泛素-蛋白酶体途径(UPP)失调所起作用方面的最新进展。