What is the role and implications of ferroptosis in pancreatic cancer?
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Ferroptosis plays a significant role in pancreatic cancer by regulating cell death, tumor growth, and drug resistance. It is closely associated with iron accumulation, lipid peroxidation, and the activity of key regulators like glutathione peroxidase 4 . Pancreatic cancer cells exhibit a strong dependence on glutamine, which can impact ferroptosis by influencing ROS formation and cell growth . Particularly in pancreatic ductal adenocarcinoma (PDAC), driven by the KRAS oncogene, ferroptosis has emerged as a crucial mechanism affecting tumor development and therapeutic responses, potentially minimizing drug resistance in clinical trials . Moreover, the interplay between diabetes-induced ferroptosis and pancreatic cancer progression highlights the complex relationship between these conditions and the potential for targeted therapies in diabetic patients .
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| Ferroptosis plays a dual role in pancreatic cancer, influencing tumor progression and treatment response. Understanding diabetes-induced ferroptosis may offer new therapeutic strategies for pancreatic cancer patients. | |
| Ferroptosis, driven by iron accumulation and lipid peroxidation, plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) by offering potential therapeutic targets to combat drug resistance and suppress tumor progression. | |
| Ferroptosis induced by glutamine deprivation inhibits pancreatic cancer growth, increases ROS, and activates ferroptosis pathways. Glutamine aids in ROS detoxification, preventing ferroptosis in pancreatic cancer cells. | |
| Ferroptosis regulates cell proliferation, reduces drug resistance, and induces cell death in pancreatic cancer. Wogonin triggers ferroptosis via the Nrf2/GPX4 axis, offering potential therapeutic benefits. | |
| Ferroptosis plays a significant role in regulating signaling pathways in pancreatic cancer, influencing tumor progression and serving as a potential therapeutic target in this gastrointestinal tumor. |
Related Questions
What is ferroptosis?4 answersFerroptosis is a form of regulated cell death characterized by the accumulation of toxic lipid peroxides, particularly in the plasma membrane, leading to lytic cell death. It is triggered by iron-dependent lipid peroxidation and is distinct from other types of cell death by function and morphology. Ferroptosis has been associated with various pathological conditions, including infection, sterile inflammation, tumor immunity, cellular metabolism, neurodegenerative diseases, cardiovascular diseases, and ischemia-reperfusion injuries. It has also been linked to cardiac diseases, with mitochondria playing a crucial role in regulating ferroptosis and protecting against mitochondrial cardiomyopathy. Additionally, ferroptosis has been implicated in autoimmune disorders, such as autoimmune hepatitis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Parkinson's Disease, psoriasis, and insulin-dependent diabetes mellitus. Targeting ferroptosis may have therapeutic potential for treating these diseases.
How does ferroptosis support tumor growth in pancreatic cancer?5 answersFerroptosis, a type of iron-dependent nonapoptotic cell death, supports tumor growth in pancreatic cancer by promoting resistance to therapy-induced apoptosis and suppressing inflammation-related immunosuppression. The exact effector molecule of ferroptosis in pancreatic cancer is still unclear, but it is believed that reactive oxygen species-induced lipid peroxidation and subsequent plasma membrane damage play a central role in mediating ferroptotic death. Glutamine, an amino acid, has been found to have a protective effect against ferroptosis in pancreatic cancer cells by decreasing reactive oxygen species formation via glutathione production. Additionally, iron metabolism and reactive oxygen species metabolism are key pathways involved in ferroptosis in pancreatic cancer. Overall, understanding the mechanisms of ferroptosis in pancreatic cancer may provide new strategies for the treatment of this highly lethal malignancy.
Under which conditions does ferroptosis support tumor growth?5 answersFerroptosis of immunosuppressive neutrophils in the tumor microenvironment blocks antitumor immunity. YY2 induces tumor cell ferroptosis and suppresses tumorigenesis by inhibiting SLC7A11 transcription, leading to decreased glutathione biosynthesis. These findings suggest that under certain conditions, ferroptosis can support tumor growth by inhibiting antitumor immunity and promoting tumorigenesis.
What is the relationship between ferroptosis and hemoglobin?5 answersFerroptosis is an iron-dependent mode of cell death that has been found to be closely related to the pathological process of many diseases, including tumors, inflammatory diseases, bacterial infections, pulmonary fibrosis, hepatitis, inflammatory bowel disease, neurodegenerative diseases, kidney injury, ischemia-reperfusion injury, and skeletal muscle injury. Hemoglobin (Hb), which is present in red blood cells, has been implicated in the process of ferroptosis. Studies have shown that heme, a component of Hb, can induce cytotoxicity and ferroptosis in herniated nucleus pulposus, leading to the progressive degeneration of lumbar discs. Additionally, in the context of hemolytic disorders and iron overload, such as in cases of anemia and transfusions of red blood cells, the increased processing and recycling of iron can create opportunities for the generation of destructive free radicals and lipid peroxidation, which are characteristic of ferroptosis. Therefore, there is a relationship between ferroptosis and hemoglobin, with Hb and its components playing a role in the induction of ferroptosis in various disease contexts.
How do DAMPs affect response to ferroptosis in pancreatic cancer?4 answersDAMPs (damage-associated molecular patterns) play a role in the response to ferroptosis in pancreatic cancer. High-iron diets or deletion of pancreatic GPX4 (glutathione peroxidase 4), a key repressor of ferroptosis, can activate the STING1/TMEM173-dependent DNA sensor pathway, accelerating the development of mutant Kras-driven PDAC (pancreatic ductal adenocarcinoma). Ferroptosis, a regulated cell death process, is involved in chemotherapy resistance and refractory to radiation therapy and immunotherapy. Diabetes-induced ferroptosis contributes to tumor cell death in pancreatic cancer, affecting various components including tumor cells, fibroblasts, immune cells, and adipocytes. Dual-specificity phosphatase 1 (DUSP1) is a new repressor of ferroptosis in human pancreatic cancer cells, and its knockdown enhances the anticancer activity of ferroptosis activators. Ferroptosis has been identified as a potential therapeutic target in PDAC, and understanding its regulatory mechanisms and signaling pathways may lead to more effective treatment designs.
Which immune cells have been studied in relation to ferroptosis?3 answersFerroptosis has been studied in relation to various immune cells.The review by Kim et al. discusses the dual role of ferroptosis in the antitumor and protumorigenic functions of immune cells in cancer.Wang and Lu's review explores the functional relationship between ferroptosis and various immune cells, as well as the role of ferroptosis in infection, inflammation, and malignancies.Oun et al. investigate the effect of LRRK2 on ferroptosis-induced cell death in immune cells, specifically using RAW macrophages.Chen et al.'s review focuses on how ferroptotic cells and their spilled contents shape innate and adaptive immunity in health and disease.Dächert et al. study the molecular mechanisms of ferroptosis in rhabdomyosarcoma (RMS) cells and the role of immune cells such as protein kinase C (PKC) and nicotinamide adenine dinucleotide phosphate-oxidase (NOX) in ferroptosis.