脂质代谢的改变被认为是结直肠癌（CRC）的标志特征。蛋白质 S-棕榈酰化在许多不同的细胞过程中发挥着关键作用，包括蛋白质-脂质相互作用。锌指 DHHC-Type Containing 1（ZDHHC1，也称为 ZNF377）属于棕榈酰转移酶 ZDHHC 家族，是一种潜在的肿瘤抑制因子。然而，我们对 ZDHHC1 在 CRC 中的功能作用的了解有限。我们发现 ZDHHC1 表达在 CRC 组织中下调，并且低水平的 ZDHHC1 与不良预后相关。功能研究表明，ZDHHC1 在体外和体内抑制 CRC 细胞增殖和侵袭。我们还发现脂肪酶 G (LIPG) 受到 ZDHHC1 的负向调节，并通过脂质储存在 CRC 细胞生长中发挥关键作用。此外，我们证明 ZDHHC1 作为 IGF2BP1 棕榈酰化酶发挥作用，诱导 IGF2BP1-C337 处的 S-棕榈酰化，从而通过 m6A 修饰下调 LIPG 表达。机制研究表明，ZDHHC1/IGF2BP1/LIPG 信号轴与抑制 CRC 细胞生长有关。我们的研究揭示了 ZDHHC1 在 CRC 中的潜在作用，包括通过 IGF2BP1 的棕榈酰化以 m6A 依赖性方式降低 LIPG mRNA 的稳定性，从而抑制 CRC 生长。© 2024。作者。

Alteration in lipid metabolism is recognized as a hallmark feature of colorectal cancer (CRC). Protein S-palmitoylation plays a critical role in many different cellular processes including protein-lipid interaction. Zinc Finger DHHC-Type Containing 1 (ZDHHC1, also known as ZNF377) belongs to the palmitoyl-transferase ZDHHC family, and is a potential tumor suppressor. However, our knowledge of the functional roles of ZDHHC1 in CRC is limited. We discovered that ZDHHC1 expression was downregulated in CRC tissues and that low levels of ZDHHC1 were associated with unfavorable prognosis. Functional studies showed that ZDHHC1 inhibited CRC cell proliferation and invasion in vitro and in vivo. We also found that lipase G (LIPG) is negatively regulated by ZDHHC1 and plays a key role in CRC cell growth through lipid storage. Additionally, we demonstrated that ZDHHC1 functions as a IGF2BP1-palmitoylating enzyme that induces S-palmitoylation at IGF2BP1-C337, which results in downregulated LIPG expression via m6A modification. Mechanistic investigations revealed that the ZDHHC1/IGF2BP1/LIPG signaling axis is associated with inhibition of CRC cell growth. Our study uncovers the potential role of ZDHHC1 in CRC, including inhibition of CRC growth by reducing the stability of LIPG mRNA in an m6A dependent-manner by palmitoylation of IGF2BP1.© 2024. The Author(s).