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

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.

• Authors: Shubin Yu, Yiwen Lu, An Su, Jianing Chen, Jiang Li, Boxuan Zhou, Xinwei Liu, Qidong Xia, Yihong Li, Jiaqian Li, Min Huang, Yingying Ye, Qiyi Zhao, Sushi Jiang, Xiaoqing Yan, Xiaojuan Wang, Can Di, Jiayao Pan, Shicheng Su
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 8 Issue 19 Pg. e2101848 (10 2021) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34363355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Histones
• Intercellular Signaling Peptides and Proteins
• osteogenic growth peptide
• SCD1 protein, human
• Stearoyl-CoA Desaturase
• Neprilysin

Topics

• Breast Neoplasms (genetics, metabolism)
• Cancer-Associated Fibroblasts (metabolism)
• China
• Female
• Histones (genetics, metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Lipid Metabolism (genetics)
• Neoplastic Stem Cells (metabolism)
• Neprilysin (genetics, metabolism)
• Signal Transduction (genetics)
• Stearoyl-CoA Desaturase (genetics, metabolism)
• Tumor Microenvironment (genetics)