dataset
posted on 2025-05-15, 12:54 authored by Shenghe Deng, Jun Wang, Falong Zou, Denglong Cheng, Mian Chen, Junnan Gu, Jianguo Shi, Jia Yang, Yifan Xue, Zhenxin Jiang, Le Qin, Fuwei Mao, Xiaona Chang, Xiu Nie, Li Liu, Yinghao Cao, Kailin Cai <p>Nontargeted metabolomics analysis of OCRC and CRC tissues</p>
Funding
2021 Clinical Research Foundation of Wuhan Union Hospital
China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)
Hubei Key Laboratory of Biological Targeted Therapy
Free Innovation Pre-Research Fund, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Natural Science Foundation of Hubei Province (湖北省自然科学基金)
History
ARTICLE ABSTRACT
Obstructions can occur during any stage of colorectal cancer and correspond with poor prognosis. Obstructive colorectal cancer (OCRC) is harder and exhibits increased tumor budding and proliferation of myofibroblasts compared with nonobstructive colorectal cancer, suggesting that the occurrence of obstruction may be related to extracellular matrix (ECM) remodeling. In this study, we found that colorectal cancer and OCRC samples differed substantially in ECM composition, specifically in collagen (newly formed and mature) and proteoglycans (including glycosaminoglycan, hyaluronic acid, and chondroitin sulfate). OCRC also exhibited considerable changes in ECM biomechanics and collagen arrangement. Interestingly, OCRC samples presented a notable increase in matrix cancer-associated fibroblasts (mCAF). The abundance of mCAFs correlated with the accumulation of palmitic acid (PA), and high concentrations of PA increased the secretion of ECM-related proteins by mCAFs. Additionally, PA did not directly affect normal fibroblasts but rather activated the NF-κB pathway in tumor cells to stimulate secretion of CSF1, TGFβ1, and CXCL8, which promoted the activation of normal fibroblasts into mCAFs and exacerbated ECM stiffening. Drug screening with a natural compound library identified vanillylacetone as a potential inhibitor of PA-induced cytokine secretion and ECM stiffening. These findings highlight intratumoral PA accumulation as a key mechanism driving ECM alterations and OCRC progression and suggest that targeting this axis may be useful for treating patients with colorectal cancer with risk of obstruction.Significance: Palmitic acid accumulation activates the NF-κB pathway in colorectal cancer cells to promote cytokine secretion that facilitates the generation of matrix cancer-associated fibroblasts, driving extracellular matrix remodeling and development of obstructions.
