The Emerging Role of Copper Metabolism and Cuproptosis in Human GI cancers

Amirali Reihani۱,۳, Alireza Samadi۲, Hossein Javid۳,۴,۵ ۱) Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. ۲) Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran. ۳) Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. ۴) Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran. ۵) Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. *Corresponding author Dr. Hossein Javid, Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran Phone: [phone] E-mail: [e-mail] ORCID: ۰۰۰۰-۰۰۰۲-۲۲۴۸-۷۷۰۸   Abstract Introduction: Gastrointestinal (GI) cancers are responsible for more than a quarter of cancer incidence globally. Despite the progression of cancer treatment, the prognosis of GI cancers is considered poor. In recent years, several metal ions have been discovered to treat cancers. Cuproptosis is a novel copper-induced mitochondrial cell death mechanism bound with the proliferation and migration of different cancers. However, the mechanisms of cuproptosis antitumor therapy have not yet been relatively understood. Method: The review article was conducted using articles from PubMed, Google Scholar, Web of Science, and Science Direct up to February ۲۰۲۴. The search terms used were Cuproptosis, Copper metabolism, and Gastrointestinal or GI cancers. This search yielded ۲۴ articles, of which ۱۵ were excluded based on their titles and abstracts. Nine articles met the inclusion criteria and were selected. All the articles that were chosen are written in English. Results: The study included a total of ۹ articles. Induction of cell death is an essential factor in cancer treatment. Copper can influence cell death through ROS, ER, inflammatory responses, etc. Copper can directly attach to lipoylated components of the tricarboxylic acid (TCA) cycle. Throughout this, the aggregation of lipoylated proteins and the subsequent loss of iron-sulfur cluster proteins happens, resulting in proteotoxic stress and ultimately concluding in cell death. Conclusion: More research in copper metabolism and cuproptosis is highly encouraged, as metal ion therapy can eliminate cancer cells with less damage to normal tissues and organs than traditional therapies. Despite the investigations developed in Ferroptosis, the death of copper-metabolism cells has not yet been relatively understood. Thus, more investigations are highly demanded.

کلیدواژه ها:

Copper metabolism ، Cuproptosis ، Gastrointestinal cancers (GI cancers)