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成纤维细胞中 CD10-OGP 膜肽酶信号轴通过 SCD1 调节肿瘤干细胞的脂质代谢。

A CD10-OGP Membrane Peptolytic Signaling Axis in Fibroblasts Regulates Lipid Metabolism of Cancer Stem Cells via SCD1.

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

出版信息

Adv Sci (Weinh). 2021 Oct;8(19):e2101848. doi: 10.1002/advs.202101848. Epub 2021 Aug 7.

DOI:10.1002/advs.202101848
PMID:34363355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8498877/
Abstract

Carcinoma-associated fibroblasts (CAFs) consist of heterogeneous subpopulations that play a critical role in the dynamics of the tumor microenvironment. The extracellular signals of CAFs have been attributed to the extracellular matrix, cytokines, cell surface checkpoints, and exosomes. In the present study, it is demonstrated that the CD10 transmembrane hydrolase expressed on a subset of CAFs supports tumor stemness and induces chemoresistance. Mechanistically, CD10 degenerates an antitumoral peptide termed osteogenic growth peptide (OGP). OGP restrains the expression of rate-limiting desaturase SCD1 and inhibits lipid desaturation, which is required for cancer stem cells (CSCs). Targeting CD10 significantly improves the efficacy of chemotherapy in vivo. Clinically, CD10-OGP signals are associated with the response to neoadjuvant chemotherapy in patients with breast cancer. The collective data suggest that a nexus between the niche and lipid metabolism in CSCs is a promising therapeutic target for breast cancer.

摘要

癌相关成纤维细胞（CAFs）由多种亚群组成，在肿瘤微环境的动态变化中发挥着关键作用。CAFs 的细胞外信号归因于细胞外基质、细胞因子、细胞表面检查点和外泌体。在本研究中，证明了在一部分 CAFs 上表达的 CD10 跨膜水解酶支持肿瘤干细胞特性并诱导化疗耐药性。从机制上讲，CD10 使一种称为成骨生长肽（OGP）的抗肿瘤肽退化。OGP 抑制限速去饱和酶 SCD1 的表达，并抑制脂质去饱和，这对于癌症干细胞（CSC）是必需的。靶向 CD10 可显著提高体内化疗的疗效。临床上，CD10-OGP 信号与乳腺癌患者新辅助化疗的反应相关。这些数据表明，CSC 中的小生境与脂质代谢之间的联系是治疗乳腺癌的一个有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/20a85a9d15bf/ADVS-8-2101848-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/8dbf6eff5985/ADVS-8-2101848-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/47574ea2522c/ADVS-8-2101848-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/b4be6fd472ff/ADVS-8-2101848-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/20a85a9d15bf/ADVS-8-2101848-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/ed941d7424a8/ADVS-8-2101848-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/333c3570758b/ADVS-8-2101848-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/3f4ab118150a/ADVS-8-2101848-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/8dbf6eff5985/ADVS-8-2101848-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/47574ea2522c/ADVS-8-2101848-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/b4be6fd472ff/ADVS-8-2101848-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0872/8498877/20a85a9d15bf/ADVS-8-2101848-g006.jpg

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2
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3
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Acta Pharm Sin B. 2025 Apr;15(4):1841-1868. doi: 10.1016/j.apsb.2025.02.040. Epub 2025 Mar 8.
4
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