CDO1 phosphorylation is required for IL-6-induced tumor cell proliferation through governing cysteine availability.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-04-23 DOI:10.1186/s12964-025-02189-w

Xin Li, Zhe Zhao, Hongping Ye, Dan Li, Xiaoke Huang, Jong-Ho Lee, Rui Liu

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引用次数: 0

Abstract

Inflammatory pathways are often hijacked by cancer cells to favor their own proliferation and survival. Cysteine dioxygenase type 1 (CDO1), an iron-dependent thiol dioxygenase enzyme, catalyzes the rate-limiting step for cysteine oxidation, and so that functions as an important regulator of cellular cysteine availability. However, whether inflammatory environment affects CDO1 activity and cysteine oxidation and its potential impact on tumor growth remains substantially elusive. In the present study, we demonstrate that CDO1 activity and cysteine oxidation is inhibited upon IL-6 treatment, without noticeable alterations in CDO1 expression. Mechanistically, AKT1 phosphorylates CDO1 T89 under IL-6 treatment, which represses CDO1 enzymatic activity by disrupting iron incorporation. Further, AKT1-mediated CDO1 T89 phosphorylation is required for IL-6-elicited oral squamous cell carcinoma (OSCC) growth, and is associated with the progression of OSCC development. The present data discover a new mechanism by which AKT1-mediated CDO1 T89 phosphorylation governs cysteine oxidation to support OSCC growth, thereby highlighting its value as a potential anti-tumor target.

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通过控制半胱氨酸的可用性，il -6诱导的肿瘤细胞增殖需要CDO1磷酸化。

炎症途径经常被癌细胞劫持，以促进自身的增殖和生存。半胱氨酸双加氧酶1 （CDO1）是一种铁依赖的硫醇双加氧酶，催化半胱氨酸氧化的限速步骤，因此它是细胞半胱氨酸可用性的重要调节因子。然而，炎症环境是否影响CDO1活性和半胱氨酸氧化及其对肿瘤生长的潜在影响仍然是一个很大的谜。在本研究中，我们证明了CDO1活性和半胱氨酸氧化在IL-6处理下被抑制，而CDO1表达没有明显改变。在机制上，AKT1在IL-6处理下磷酸化CDO1 T89，通过破坏铁结合抑制CDO1酶活性。此外，akt1介导的CDO1 T89磷酸化是il -6诱导的口腔鳞状细胞癌（OSCC）生长所必需的，并且与OSCC发展的进展有关。目前的数据发现了akt1介导的CDO1 T89磷酸化控制半胱氨酸氧化以支持OSCC生长的新机制，从而突出了其作为潜在抗肿瘤靶点的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.