A novel SOX6 + melanoma cell subtype promotes early microsatellite invasion in Asian acral melanoma through fatty acid transport disorder.

IF 12.8 1区 医学 Q1 ONCOLOGY
Chuan Lv, Kexin Chen, Tengjiao Wang, Junfeng Jiang, Guanghui Hu, Jianan Gu, Tao Liu, Sheng Wang, Haiying Dai, Yue Wang
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引用次数: 0

Abstract

Acral melanoma (AM) is the predominant subtype of melanoma in Asians. Early detection and prevention can significantly improve patient outcomes; however, there is a lack of effective early biomarkers for predicting AM metastasis. Here, we employed single-cell and spatial transcriptomics analyses to investigate early microsatellite lesions of AM and identify biomarkers of invasiveness in these lesions. Our results characterize a highly immunosuppressive microenvironment and metabolic process shifts in early AM microsatellite lesions that promote the metastatic potential. The transcription factor SOX6 is overexpressed in microsatellite lesions and marks a population of highly invasive melanoma cells. The pro-invasive role of overexpressed SOX6 was validated in vivo and in vitro, including its ability to enhance tumor invasion by upregulating cellular glycolysis, disrupt fatty acid transport, and increase intracellular phosphatidylcholine content. This study suggests that SOX6-overexpressing melanoma cells are the main driver subpopulation promoting early invasion of AM and establishes SOX6 and fatty acid transport processes as biomarkers and potential therapeutic targets for early melanoma metastasis.

一种新的SOX6 +黑色素瘤细胞亚型通过脂肪酸运输障碍促进亚洲肢端黑色素瘤的早期微卫星侵袭。
肢端黑色素瘤(AM)是亚洲黑色素瘤的主要亚型。早期发现和预防可以显著改善患者的预后;然而,缺乏有效的早期生物标志物来预测AM转移。在这里,我们采用单细胞和空间转录组学分析来研究AM的早期微卫星病变,并确定这些病变中侵袭性的生物标志物。我们的研究结果描述了早期AM微卫星病变中高度免疫抑制的微环境和代谢过程的变化,这些变化促进了转移潜力。转录因子SOX6在微卫星病变中过度表达,并标志着高度侵袭性黑色素瘤细胞的群体。过表达的SOX6的促侵袭作用在体内和体外都得到了验证,包括通过上调细胞糖酵解、破坏脂肪酸运输和增加细胞内磷脂酰胆碱含量来增强肿瘤侵袭的能力。本研究提示过表达SOX6的黑色素瘤细胞是促进AM早期侵袭的主要驱动亚群,并建立了SOX6和脂肪酸转运过程作为早期黑色素瘤转移的生物标志物和潜在治疗靶点。
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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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