Regulation of Nrf2/Keap1 signaling pathway in cancer drug resistance by galectin-1:cellular and molecular implications  

作　　者：İlhan Yaylim Melek Aru Ammad Ahmad Farooqi Mehmet Tolgahan Hakan Brigitta Buttari Marzia Arese Luciano Saso 

机构地区：[1]Department of Molecular Medicine,Aziz Sancar Institute of Experimental Medicine,Istanbul University,Istanbul 34280,Turkiye [2]Department of Medical Education,Istinye University Faculty of Medicine,Istanbul 34396,Turkiye [3]Institute of Biomedical and Genetic Engineering(IBGE),Islamabad 54000,Pakistan [4]Department of Cardiovascular and Endocrine-Metabolic Diseases,and Aging,Italian National Institute of Health,Rome 00161,Italy [5]Department of Biochemical Sciences“A.Rossi Fanelli”,Sapienza University,Rome 00185,Italy [6]Department of Physiology and Pharmacology“Vittorio Erspamer”,Sapienza University,Rome 00185,Italy

出　　处：《Cancer Drug Resistance》2024年第1期940-955,共16页癌症耐药(英文)

摘　　要：Oxidative stress is characterized by the deregulation of the redox state in the cells,which plays a role in the initiation of various types of cancers.The activity of galectin-1(Gal-1)depends on the cell redox state and the redox state of the microenvironment.Gal-1 expression has been related to many different tumor types,as it plays important roles in several processes involved in cancer progression,such as apoptosis,cell migration,adhesion,and immune response.The erythroid-2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)signaling pathway is a crucial mechanism involved in both cell survival and cell defense against oxidative stress.In this review,we delve into the cellular and molecular roles played by Gal-1 in the context of oxidative stress onset in cancer cells,particularly focusing on its involvement in activating the Nrf2/Keap1 signaling pathway.The emerging evidence concerning the anti-apoptotic effect of Gal-1,together with its ability to sustain the activation of the Nrf2 pathway in counteracting oxidative stress,supports the role of Gal-1 in the promotion of tumor cells proliferation,immuno-suppression,and anti-tumor drug resistance,thus highlighting that the inhibition of Gal-1 emerges as a potential strategy for the restraint and regression of tumor progression.Overall,a deeper understanding of the multi-functionality and disease-specific expression profiling of Gal-1 will be crucial for the design and development of novel Gal-1 inhibitors as anticancer agents.Excitingly,although it is still understudied,the ever-growing knowledge of the sophisticated interplay between Gal-1 and Nrf2/Keap1 will enable researchers to gain valuable insights into the underlying causes of carcinogenesis and metastasis.

关 键 词：GALECTIN-1 NRF2 oxidative stress cancer drug resistance 

分 类 号：R73[医药卫生—肿瘤]