近日，北京大学教授孙璐璐及其团队的论文报道了微生物核黄素抑制神经酰胺合成酶3降低神经酰胺（d18:1/26:0）并延迟结直肠癌癌症。这一研究成果发表在2025年7月2日出版的国际学术期刊《细胞—代谢》上。

该课题组发现纤维素拟杆菌的丰度通过产生抑制CERS3活性的核黄素来影响肿瘤的异质性，从而延缓CRC的进展。

此外， FDA批准的药物aclidinium bromide对CERS3活性有显著的抑制作用，提示其在结直肠癌治疗中的潜在应用。这些发现阐明了神经酰胺对CRC影响的代谢途径和机制，强调靶向CERS3抑制是一种有希望的CRC治疗策略。

据悉，神经酰胺代谢失调与结直肠癌（CRC）进展有关，但机制尚不清楚。d18:1/26:0神经酰胺（C26）水平在CRC患者和motheme模型中升高，其通过结合表皮生长因子受体（EGFR）的细胞外区域激活其，促进癌细胞增殖。C26水平升高主要是由于神经酰胺合成酶3 （CERS3）活性升高所致。高表达的CERS3通常会加速肿瘤进展，但一些患者表现出显著的异质性，表明内源性代谢产物可影响CERS3活性。

附：英文原文

Title: Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression

Author: Ruize Qu, Yi Zhang, Bora Kim, Guangyi Zeng, Pengcheng Wang, Weike Shaoyong, Ying Huang, Wanwan Guo, Yang Chen, Ping Wang, Qing Yang, Siyi Lu, Xin Zhou, Jing Weng, Jinkun Xu, Jun Lin, Kai Wang, Yanpeng Ma, Shogo Takahashi, Yuhong Luo, Xiaoting Yu, Kristopher W. Krausz, Yanli Pang, Tianpei Hong, Zhipeng Zhang, Wei Fu, Frank J. Gonzalez, Lulu Sun

Issue&Volume: 2025-07-02

Abstract: Ceramide metabolism dysregulation links to colorectal cancer (CRC) progression, yet the mechanism remains unknown. d18:1/26:0 ceramide (C26) levels were elevated in patients with CRC and mouse models, which activated epidermal growth factor receptor (EGFR) by binding its extracellular region to promote cancer cell proliferation. The rise of C26 levels was mainly driven by heightened ceramide synthase 3 (CERS3) activity. High CERS3 expression generally accelerated tumor progression, yet some patients exhibited significant heterogeneity, suggesting endogenous metabolites available to affect CERS3 activity. We found that the abundance of Bacteroides cellulosilyticus affects tumor heterogeneity by producing riboflavin that inhibits CERS3 activity, thus delaying CRC progression. Moreover, aclidinium bromide, an FDA-approved drug, exhibited significant inhibitory effects on CERS3 activity, suggesting its potential application in CRC treatment. These findings elucidate the metabolic pathways and mechanisms underlying ceramide’s impact on CRC, highlighting that targeting CERS3 inhibition represents a promising therapeutic strategy for CRC.

DOI: 10.1016/j.cmet.2025.06.002

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00297-9