Single-cell multi-omics reveals that FABP1 + renal cell carcinoma drive tumor angiogenesis through the PLG-PLAT axis under fatty acid reprogramming.

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-06-16 DOI:10.1186/s12943-025-02377-9

Yiqiu Wang,Yingchun Liang,Min Li,Jiayi Lu,Sian Zhou,Yaoyu Yu,Changwei Yang,Xinhuang Hou

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引用次数: 0

Abstract

Renal cell carcinoma is characterized by a poor prognosis. Recently, renal cell carcinoma has been recognized as a metabolic disease associated with fatty acid metabolic reprogramming, although in-depth studies on this topic are still lacking. We found that fatty acid metabolism reprogramming in renal cell carcinoma is primarily characterized by high expression of FABP1. FABP1 + tumors significantly impact survival and display distinct differentiation trajectories compared to other tumor subclusters. They show elevated expression of angiogenesis and cell migration signals, with PLG-PLAT-mediated interactions with endothelial cells notably enhanced. Spatial transcriptomics show a prominent co-localization of FABP1 + tumors with endothelial cells, and their spatial distribution closely aligns with that of PLAT + endothelial cells. FABP1 + tumors exhibit a unique pattern in spatial transcriptomics, enriched in Extracellular Matrix and angiogenesis-related pathways. Through receptor-ligand interaction analysis, a novel PLG-PLAT functional axis was found between tumor epithelial cells and endothelial cells. Based on results of experiments, we infer that FABP1 + tumors can promote plasmin-related tumor angiogenesis by triggering the PLG-PLAT signaling axis. Finally, utilizing preclinical models, we suggest that targeting the FABP1-PLG-PLAT axis may serve as promising strategy enhancing the sensitivity of Tyrosine Kinase Inhibitor therapy.

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单细胞多组学表明，FABP1 +肾细胞癌在脂肪酸重编程下通过PLG-PLAT轴驱动肿瘤血管生成。

肾细胞癌的特点是预后不良。近年来，肾细胞癌被认为是一种与脂肪酸代谢重编程相关的代谢性疾病，但目前还缺乏深入的研究。我们发现，在肾细胞癌中，脂肪酸代谢重编程主要以FABP1的高表达为特征。与其他肿瘤亚群相比，FABP1 +肿瘤显著影响生存，并表现出不同的分化轨迹。它们表现出血管生成和细胞迁移信号的表达升高，plg - plat介导的与内皮细胞的相互作用明显增强。空间转录组学显示，FABP1 +肿瘤与内皮细胞有明显的共定位，其空间分布与PLAT +内皮细胞的空间分布密切一致。FABP1 +肿瘤在空间转录组学中表现出独特的模式，富含细胞外基质和血管生成相关途径。通过受体-配体相互作用分析，在肿瘤上皮细胞和内皮细胞之间发现了一条新的PLG-PLAT功能轴。根据实验结果，我们推断FABP1 +肿瘤可通过触发PLG-PLAT信号轴促进纤溶蛋白相关肿瘤血管生成。最后，利用临床前模型，我们建议靶向FABP1-PLG-PLAT轴可能是提高酪氨酸激酶抑制剂治疗敏感性的有希望的策略。

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

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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