GPR37 promotes colorectal cancer against ferroptosis by reprogramming lipid metabolism via p38-SCD1 axis

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jiamin Zhou, Xigan He, Weixing Dai, Qingguo Li, Zhen Xiang, Yixiu Wang, Ti Zhang, Weiqi Xu, Lu Wang, Anrong Mao
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引用次数: 0

Abstract

Colorectal cancer (CRC) is a prevalent malignant tumor worldwide, leading to significant morbidity and disease burden. Diagnostic indicators and treatment objectives for CRC are urgently needed. This study demonstrates that GPR37, a GPCR receptor, is highly expressed in CRC. Depletion of GPR37 significantly reduced CRC tumor cell growth both in vitro and in vivo. Further tests showed that GPR37 protects cancer cells from ferroptosis by upregulating SCD1 expression, thereby modulating lipid metabolism, suppressing the level of reactive oxygen species, and mitigating ferroptosis. Mechanistic studies have shown that GPR37 modulates lipid metabolism in tumor cells by promoting SCD1 transcription via the MAPK-p38 signaling pathway. Our results reveal the pro-carcinogenic effect of GPR37 in primary CRC and suggest that targeting GPR37 could be a potential therapeutic target for CRC.

GPR37 通过 p38-SCD1 轴重塑脂质代谢,促进结直肠癌对抗铁变态反应。
结肠直肠癌(CRC)是全球流行的恶性肿瘤,会导致严重的发病率和疾病负担。目前迫切需要针对 CRC 的诊断指标和治疗目标。这项研究表明,GPR37 是一种 GPCR 受体,在 CRC 中高度表达。删除 GPR37 可显著降低 CRC 肿瘤细胞在体外和体内的生长。进一步的测试表明,GPR37 通过上调 SCD1 的表达,从而调节脂质代谢,抑制活性氧水平,减轻铁变态反应,保护癌细胞免受铁变态反应的影响。机理研究表明,GPR37 通过 MAPK-p38 信号通路促进 SCD1 转录,从而调节肿瘤细胞的脂质代谢。我们的研究结果揭示了 GPR37 在原发性 CRC 中的促癌作用,并表明靶向 GPR37 可能是 CRC 的潜在治疗靶点。
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
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
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