The biological significance of carbohydrate responsive element binding protein in response to cellular stress

• Main Authors: Ya-RouDing, 丁雅柔
• Other Authors: Nan-Haw Chow
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/63141214383481060902

碩士 === 國立成功大學 === 分子醫學研究所 === 101 === Human body is exposed to different biological stresses from external and internal environments. Normal cellular responses to stress are important barriers to carcinogenesis. These cellular stresses and evasion of apoptosis are important biological characteristics of tumorigenesis. Our recent study demonstrated that over-expression of receptor tyrosine kinase-RON may provide human cancer cells with stress adaptation advantage by functioning as a transcriptional activator. The carbohydrate responsive element binding protein (ChREBP) belongs to bHLH/LZ transcription factor family, and was reported to regulate several genes related to lipogenesis and glycolysis. ChREBP was one of the candidate target genes for nuclear RON in response to serum starvation in human bladder cancer. We demonstrated that ChREBP is ubiquitously expressed in human uroepithelial cells and liver cancer cell lines, with a trend toward down-regulation in the progression of hepatocarcinogenesis. Most of ChREBP was localized to the cytosol in the absence of glucose, and translocated into nucleus after glucose supplement. In contrast, ChREBP was translocated into nucleus in response to serum starvation, hypoxic stress and growth factor stimulation onto cancer cells. Taken together, ChREBP not only functions as a glucose-sensing protein but also a stress-response protein. Overexpression and/or activation of ChREBP promote the proliferation, migration and anchorage-independent growth. ChREBP may play a positive role in the cancer progression and thus deserves to be investigated as a therapeutic target in the treatment of cancer in the future.