Ferritinophagy is a form of selective autophagy responsible for degrading intracellular ferritin, mediated by nuclear receptor coactivator 4 (NCOA4). NCOA4 plays significant roles in systemic iron homeostasis, and its disruption leads to simultaneous anemia and susceptibility to iron overload. The importance of iron colorectal cancer pathogenesis is well studied; however, the role of ferritinophagy in colon cancer cell growth has not been assessed. Disruption of ferritinophagy via NCOA4 knockout leads to only marginal differences in growth under basal and iron‐restricted conditions. Moreover, NCOA4 played no significant role in cell death induced by 5‐fluorouracil and erastin. Western blotting analysis for ferritin and transferrin receptor 1 found a dose‐dependent effect on expression in both proteins in wild‐type and NCOA4 knockout cell lines, but further investigation revealed no difference in growth response when treated at both high and low doses. Our data demonstrate a marginal role for ferritinophagy in growth both under normal and cytotoxic conditions in colon cancer cells, as well as a possible compensatory mechanism in colon cancer cells in response to ferroptosis induction.

中文翻译：

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结肠癌细胞的生长不需要铁蛋白吞噬。

铁蛋白吞噬是一种选择性自噬的形式，负责降解细胞内铁蛋白，由核受体共激活因子4（NCOA4）介导。NCOA4在系统性铁稳态中起重要作用，其破坏导致同时性贫血和对铁超负荷的敏感性。铁结直肠癌发病机理的重要性已得到充分研究。然而，尚未评估铁蛋白吞噬在结肠癌细胞生长中的作用。通过NCOA4敲除破坏铁蛋白吞噬仅导致在基础和铁限制条件下生长的边际差异。此外，NCOA4在5-氟尿嘧啶和ERAstin诱导的细胞死亡中不发挥重要作用。对铁蛋白和转铁蛋白受体1的蛋白质印迹分析发现，野生型和NCOA4敲除细胞系中的蛋白质表达均呈剂量依赖性，但是进一步的研究表明，无论高剂量还是低剂量，其生长反应均无差异。我们的数据表明，在正常和细胞毒性条件下，结肠癌细胞中铁蛋白吞噬作用在生长中的边际作用，以及结肠铁细胞对铁素体病诱导的响应的可能的补偿机制。