Targeting Notch degradation system provides promise for breast cancer therapeutics.
Notch receptor signaling pathways play an important role, not only in normal breast development but also in breast cancer development and progression. As a group of ligand-induced proteins, different subtypes of mammalian Notch (Notch1-4) are sensitive to subtle changes in protein levels. Thus, a clear understanding of mechanisms of Notch protein turnover is essential for understanding normal and pathological mechanisms of Notch functions. It has been suggested that there is a close relationship between the carcinogenesis and the dysregulation of Notch degradation. However, this relationship remains mostly undefined in the context of breast cancer, as protein degradation is mediated by numerous signaling pathways as well as certain molecule modulators (activators/inhibitors). In this review, we summarize the published data regarding the regulation of Notch family member degradation in breast cancer, while emphasizing areas that are likely to provide new therapeutic modalities for mechanism-based anti-cancer drugs.
Chang Jiang Scholar's Laboratory, Shantou University Medical College, Shantou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China. Electronic address: jliu12@stu.edu.cn.
Jing
J
Liu
Chang Jiang Scholar's Laboratory, Shantou University Medical College, Shantou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China. Electronic address: luke1989shen@163.com.
Jia-Xin
JX
Shen
Chang Jiang Scholar's Laboratory, Shantou University Medical College, Shantou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China. Electronic address: 517826771@qq.com.
Xiao-Fen
XF
Wen
Chang Jiang Scholar's Laboratory, Shantou University Medical College, Shantou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China. Electronic address: 359725929@qq.com.
Yu-Xian
YX
Guo
Chang Jiang Scholar's Laboratory, Shantou University Medical College, Shantou, Guangdong Province, PR China; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, PR China. Electronic address: guoj_zhang@yahoo.com.
Guo-Jun
GJ
Zhang
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008024:Ligands; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D054875:Ubiquitination
D008024:Ligands; D051880:Receptors, Notch
Breast cancer; Degradation; Notch; Therapy; Ubiquitin-proteasome system