Fibroblast-derived POSTN promotes colorectal cancer progression under high-fat diet by reprogramming fatty acid metabolism in tumor cell

Sep 22, 2026

Upload by Patrick

Abnormal POSTN expression is closely tied to cancer development, particularly colorectal cancer (CRC), yet its roles and mechanisms in high-fat diet (HFD)-driven CRC progression remain insufficiently defined. POSTN effects were evaluated in vitro and in vivo, with dynamic lipid-metabolizing enzyme expression changes analyzed. Molecular and biological experiments indicate POSTN modulates fat accumulation and fatty acid oxidation (FAO) dysregulation. POSTN was elevated in CRC patients, associated with poor prognosis via myCAF, and fibroblast-derived POSTN promoted SREBP1 through AKT while suppressing CPT1A-mediated FAO via ERK; the POSTN receptor CD51 inhibitor Cilengitide reduced CRC proliferation under HFD.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

Li etal. Cell Communication and Signaling (2026) 24:91 [https://doi.org/10.1186/s12964-025-02618-w](https://doi.org/10.1186/s12964-025-02618-w) Cell Communication and Signaling RESEARCH Open Access Fibroblast-derived POSTN promotes colorectal cancer progression under high-fat diet by reprogramming fatty acid metabolism in tumor cell Biao Li1†, Shasha Hou2†, Tian Tian3†, Shuai Yuan4, Anrui Li5, Yao Feng6, Zhuoxi Liu7, Jing Mi1, Zhengyi Cheng8, Shengnan Lv1, Jiajun Yang1, Yiming Lu9, Xinlai Qi9, Shiqi Song9, Zijuan Zha9 and Qi Yuan1* Abstract Abnormal expression of POSTN is closely related to the development of cancer, especially in colorectal cancer (CRC) . However, the effects and mechanisms of POSTN on CRC progression under high-fat diet (HFD) have not been thoroughly studied. The effect of POSTN on HFD-induced CRC was evaluated in vitro and in vivo, and the dynamic changes of different lipid metabolizing enzyme expression were analyzed. Molecular and biological experiments have revealed the underlying mechanisms of POSTN regulating the production of fat accumulation and fatty acid oxidation (FAO) dysregulation. POSTN expression was significantly increased in CRC patients, and was correlated with clinical poor prognosis, mainly derived from myCAF. Deletion of fibroblast-derived POSTN inhibits CRC progression under HFD. Mechanistically, fibroblast-derived POSTN promotes the expression of SREBP1 in tumor cells by regulating the AKT signaling pathway, thereby promoting fatty acid (FA) synthesis. At the sametime, fibroblast-derived POSTN inhibits the activity of FAO-related enzyme CPT1A in tumor cells through the ERK signaling pathway, thus inhibiting the FAO process. In addition, we found that CD51 (POSTN receptor) inhibitor Cilengitide effectively inhibits abnormal proliferation of CRC cells, thereby inhibiting tumor development in the HFD environment. Keywords POSTN, Colorectal cancer, Fatty acid metabolism, SREBP1, CPT1A †Biao Li, Shasha Hou and Tian Tian contributed equally to this work. *Correspondence: Qi Yuan [yuanqi@mdjmu.edu.cn](yuanqi@mdjmu.edu.cn) 1College of Life Sciences, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang 157011, China 2Department of Life Science and Engineering, Jining University, Jining, China 3College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, China 4School of Basic Medicine, Qiqihar Medical University, Qiqihar, China 5Department of urology, Harbin Medical University Cancer Hospital, Harbin, China 6Clinical Medical School, Jiamusi University, Jiamusi, China 7The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, China 8Department of Pathology, The Affiliated Hospital of Northwest University, Xi’an No.3 Hospital, Xi’an, China 9School of Basic Medicine, Mudanjiang Medical University, Mudanjiang, China © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommo

FAQs

How was POSTN’s role in high-fat diet-induced colorectal cancer assessed?

POSTN effects were evaluated using in vitro and in vivo models, and dynamic changes in lipid-metabolizing enzyme expression were analyzed.

What mechanism explains how fibroblast-derived POSTN alters fatty acid metabolism in tumor cells?

Fibroblast-derived POSTN promotes SREBP1 expression via AKT signaling to enhance fatty acid synthesis and inhibits FAO by suppressing the CPT1A activity through ERK signaling.

What clinical and cellular evidence links POSTN to CRC prognosis and myCAF?

POSTN expression was significantly increased in CRC patients and correlated with poor prognosis, mainly derived from myCAF, while deletion of fibroblast-derived POSTN inhibited CRC progression under HFD.

Sep 22, 2026

Upload by Patrick