Yu Yu-Qiang, Gamez-Belmonte Reyes, Patankar Jay V, Liebing Eva, Becker Christoph
Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany.
Cancers (Basel). 2022 Sep 1;14(17):4295. doi: 10.3390/cancers14174295.
For quite a long time, necrosis was considered a chaotic and unorganized form of cell death. However, studies conducted during the past few decades unveiled multiple types of programmed necrosis, such as necroptosis, pyroptosis and ferroptosis. These types of programmed necrosis have been shown to play crucial roles in mediating pathological processes, including tumorigenesis. Almost all key mediators, such as RIPK3 and MLKL in necroptosis, GSDMD and caspase 1/11 in pyroptosis and GPX4 in ferroptosis, are highly expressed in intestinal epithelial cells (IECs). An aberrant increase or decrease in programmed necrosis in IECs has been connected to intestinal disorders. Here, we review the pathways of programmed necrosis and the specific consequences of regulated necrosis in colorectal cancer (CRC) development. Translational aspects of programmed necrosis induction as a novel therapeutic alternative against CRC are also discussed.
在相当长的一段时间里，坏死被认为是一种混乱无序的细胞死亡形式。然而，过去几十年进行的研究揭示了多种程序性坏死类型，如坏死性凋亡、炎性小体介导的细胞焦亡和铁死亡。这些程序性坏死类型已被证明在介导包括肿瘤发生在内的病理过程中发挥关键作用。几乎所有关键介质，如坏死性凋亡中的RIPK3和MLKL、炎性小体介导的细胞焦亡中的GSDMD和caspase 1/11以及铁死亡中的GPX4，在肠上皮细胞（IECs）中均高表达。IECs中程序性坏死的异常增加或减少与肠道疾病有关。在此，我们综述了程序性坏死的途径以及调节性坏死在结直肠癌（CRC）发生发展中的具体后果。还讨论了诱导程序性坏死作为一种针对CRC的新型治疗选择的转化方面。
