Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Apoptosis. 2024 Dec;29(11-12):1988-2001. doi: 10.1007/s10495-024-02018-4. Epub 2024 Sep 21.
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.
结直肠癌（CRC）是一种常见的恶性肿瘤，在全球范围内导致了严重的发病率和疾病负担。CRC 的诊断指标和治疗目标亟待明确。本研究表明，GPCR 受体 GPR37 在 CRC 中高表达。GPR37 耗竭显著抑制 CRC 肿瘤细胞的体外和体内生长。进一步的实验表明，GPR37 通过上调 SCD1 的表达来保护癌细胞免受铁死亡，从而调节脂质代谢，抑制活性氧水平，并减轻铁死亡。机制研究表明，GPR37 通过 MAPK-p38 信号通路促进 SCD1 转录来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 中的致癌作用，并表明靶向 GPR37 可能是 CRC 的一个潜在治疗靶点。
