Department of Tumor Biological Diagnosis and Treatment Center, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.
Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.
J Transl Med. 2024 May 27;22(1):510. doi: 10.1186/s12967-024-05277-6.
Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior. Recent studies indicate that various molecular pathways, including the dysregulation of ferredoxin 1 (FDX1), play roles in LUAD progression. FDX1, a crucial protein in cellular redox reactions and energy metabolism, has been linked to several cancers. However, its exact role in the development of LUAD is not yet fully understood.
We investigated the role of ferredoxin 1 (FDX1) in LUAD progression through analysis of its expression in LUAD tissues and its impact on patient survival. Functional assays were performed to assess the effects of FDX1 overexpression on LUAD cell proliferation, migration, and invasion. A xenograft model was employed to evaluate the tumorigenesis potential of LUAD cells with FDX1 overexpression. Mechanistic insights into FDX1 regulation were gained through depletion experiments targeting the G protein-regulated inducer of neurite outgrowth 2 (GPRIN2)/PI3K signaling pathway.
FDX1 expression was down-regulated in LUAD tissues, correlating with shorter patient survival. Overexpression of FDX1 suppressed LUAD cell proliferation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Mechanistically, the GPRIN2/PI3K signaling pathway was implicated in FDX1 regulation, as depletion of GPRIN2 reversed the effects of FDX1 overexpression on cellular functions.
Our findings highlight FDX1 as a potential tumor suppressor in LUAD, acting through modulation of the GPRIN2/PI3K signaling pathway. These results suggest FDX1 as a promising therapeutic target for LUAD treatment, warranting further investigation into its clinical relevance.
肺腺癌（LUAD）是一种高度致命的肺癌形式。尽管在治疗方面取得了进展，但由于其侵袭性行为，管理 LUAD 仍然具有挑战性。最近的研究表明，包括铁氧还蛋白 1（FDX1）失调在内的各种分子途径在 LUAD 进展中发挥作用。FDX1 是细胞氧化还原反应和能量代谢中的关键蛋白，与多种癌症有关。然而，其在 LUAD 发展中的确切作用尚未完全了解。
我们通过分析 FDX1 在 LUAD 组织中的表达及其对患者生存的影响，研究了 FDX1 在 LUAD 进展中的作用。进行了功能测定，以评估 FDX1 过表达对 LUAD 细胞增殖、迁移和侵袭的影响。采用异种移植模型评估过表达 FDX1 的 LUAD 细胞的致瘤潜力。通过针对 G 蛋白调节的神经突生长诱导因子 2（GPRIN2）/PI3K 信号通路的耗竭实验，获得了 FDX1 调节的机制见解。
FDX1 在 LUAD 组织中表达下调，与患者生存时间缩短相关。FDX1 过表达在体外抑制 LUAD 细胞增殖、迁移和侵袭，并抑制体内肿瘤发生。在机制上，GPRIN2/PI3K 信号通路参与了 FDX1 的调节，因为 GPRIN2 的耗竭逆转了 FDX1 过表达对细胞功能的影响。
我们的研究结果强调了 FDX1 作为 LUAD 中的潜在肿瘤抑制因子的作用，通过调节 GPRIN2/PI3K 信号通路发挥作用。这些结果表明 FDX1 作为 LUAD 治疗的有前途的治疗靶点，值得进一步研究其临床相关性。
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