03 April 2024 | Feilong Chen, Mei Xiao, Shaofan Hu, Meng Wang
The Keap1-Nrf2 signaling pathway is a critical regulator of cellular protection against oxidative and electrophilic stress, involving endogenous and exogenous stress caused by reactive oxygen species (ROS). Nrf2 is the core component of this pathway, which can be activated or inhibited by various mechanisms, including transcriptional, epigenetic, and ARE-binding regulation. Keap1, a negative regulator of Nrf2, is composed of several domains and is involved in the ubiquitination and degradation of Nrf2 through the ubiquitin proteasome pathway. The Keap1-Nrf2 pathway acts as a double-edged sword, protecting cells from oxidative stress while also promoting cancer cell survival and proliferation. Oxidative stress is considered a marker of cancer, and the Keap1-Nrf2 pathway is abnormal in various human malignant tumors, such as lung, liver, and thyroid cancer. Recent research has deepened the understanding of this pathway, highlighting its potential as a therapeutic target for cancer prevention and treatment. The article reviews the structure, function, and clinical application status of the Keap1-Nrf2 pathway, emphasizing its role in carcinogenesis and the development of cancer.The Keap1-Nrf2 signaling pathway is a critical regulator of cellular protection against oxidative and electrophilic stress, involving endogenous and exogenous stress caused by reactive oxygen species (ROS). Nrf2 is the core component of this pathway, which can be activated or inhibited by various mechanisms, including transcriptional, epigenetic, and ARE-binding regulation. Keap1, a negative regulator of Nrf2, is composed of several domains and is involved in the ubiquitination and degradation of Nrf2 through the ubiquitin proteasome pathway. The Keap1-Nrf2 pathway acts as a double-edged sword, protecting cells from oxidative stress while also promoting cancer cell survival and proliferation. Oxidative stress is considered a marker of cancer, and the Keap1-Nrf2 pathway is abnormal in various human malignant tumors, such as lung, liver, and thyroid cancer. Recent research has deepened the understanding of this pathway, highlighting its potential as a therapeutic target for cancer prevention and treatment. The article reviews the structure, function, and clinical application status of the Keap1-Nrf2 pathway, emphasizing its role in carcinogenesis and the development of cancer.