Breast cancer originates primarily from the epithelial cells of the mammary gland.Repeated mammary gland expansion and degeneration are accompanied by an increased risk of genetic alterations in the breast1.These muta...Breast cancer originates primarily from the epithelial cells of the mammary gland.Repeated mammary gland expansion and degeneration are accompanied by an increased risk of genetic alterations in the breast1.These mutations in breast epithelial cells dynamically occur in response to pregnancy,labor and delivery,breastfeeding,and the menstrual cycle,with a decline in mutation rates after menopause,which may be related to a decrease in estrogen levels.The breast epithelial cell mutations are also consistent with epidemiologic observations2.展开更多
The NOTCH gene was identified approximately 110 years ago.Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway.NOTCH receptors undergo three cleavages and translocate into the nu...The NOTCH gene was identified approximately 110 years ago.Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway.NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes.NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs,the aberration of which results in cancerous and noncancerous diseases.However,recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context.In terms of cancers,NOTCH signaling can both promote and inhibit tumor development in various types of cancer.The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations.Additionally,NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers.Collectively,the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications.In this review,we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history,architecture,regulatory mechanisms,contributions to physiological development,related diseases,and therapeutic applications of the NOTCH pathway.The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted.We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China (Grant No.32171363)the Fujian Major Scientific and Technological Special Project for Social Development (Grant No.2020YZ016002)+2 种基金the Science and Technology Project of Xiamen Municipal Bureau of Science and Technology (Grant No.3502Z20199047)the Xiamen’s Key Laboratory of Precision Medicine for Endocrine-Related Cancers (Grant No.XKLEC 2020KF02)the Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer。
文摘Breast cancer originates primarily from the epithelial cells of the mammary gland.Repeated mammary gland expansion and degeneration are accompanied by an increased risk of genetic alterations in the breast1.These mutations in breast epithelial cells dynamically occur in response to pregnancy,labor and delivery,breastfeeding,and the menstrual cycle,with a decline in mutation rates after menopause,which may be related to a decrease in estrogen levels.The breast epithelial cell mutations are also consistent with epidemiologic observations2.
基金the National Natural Science Foundation of China(No.62131009,82072597,81874120,and 82073370).
文摘The NOTCH gene was identified approximately 110 years ago.Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway.NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes.NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs,the aberration of which results in cancerous and noncancerous diseases.However,recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context.In terms of cancers,NOTCH signaling can both promote and inhibit tumor development in various types of cancer.The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations.Additionally,NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers.Collectively,the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications.In this review,we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history,architecture,regulatory mechanisms,contributions to physiological development,related diseases,and therapeutic applications of the NOTCH pathway.The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted.We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.
