心脏病和癌症是工业化国家发病率和死亡率的两个主要原因，它们日益被认识到的联系正在将重点从单一疾病研究转向跨学科研究。成纤维细胞介导的细胞间相互交流在这两种病理演变中至关重要。在健康的心肌和非癌症状态下，驻留成纤维细胞是合成细胞外基质（ECM）的主要细胞来源，并且是组织完整性的重要哨兵。在心肌疾病或癌症的环境下，静止的成纤维细胞分别激活为肌成纤维细胞（myoFbs）和癌相关成纤维细胞（CAFs），表现为收缩蛋白的产生增加以及高度增殖和分泌性表型。尽管myoFbs / CAFs的初始激活是修复损伤组织的适应性过程，但ECM蛋白的大量沉积导致了不适应性的心脏或癌症纤维化，这是不良预后的可认可标志。更好地理解编排成纤维细胞过度活跃的关键机制可能有助于开发创新的治疗选项，以限制心肌或肿瘤的硬度并改善患者预后。尽管仍不为人所知，心肌和肿瘤成纤维细胞向myoFbs和CAFs的动态转换共享几个共同的触发器和信号通路，这些通路与TGF-β依赖级联、代谢重编程、机械转导、分泌特性和表观遗传调控相关，这可能为未来的抗纤维化干预打下基础。因此，本综述的目的是突出在myoFbs和CAFs激活的分子标志中出现的新兴类比，以便确定新的预后/诊断生物标志物，并阐明药物复用策略消除心脏/癌症纤维化的潜力。版权所有©2023 Elsevier Inc. 发表。

Heart disease and cancer are two major causes of morbidity and mortality in the industrialized countries, and their increasingly recognized connections are shifting the focus from single disease studies to an interdisciplinary approach. Fibroblast-mediated intercellular crosstalk is critically involved in the evolution of both pathologies. In healthy myocardium and in non-cancerous conditions, resident fibroblasts are the main cell source for synthesis of the extracellular matrix (ECM) and important sentinels of tissue integrity. In the setting of myocardial disease or cancer, quiescent fibroblasts activate, respectively, into myofibroblasts (myoFbs) and cancer-associated fibroblasts (CAFs), characterized by increased production of contractile proteins, and by a highly proliferative and secretory phenotype. Although the initial activation of myoFbs/CAFs is an adaptive process to repair the damaged tissue, massive deposition of ECM proteins leads to maladaptive cardiac or cancer fibrosis, a recognized marker of adverse outcome. A better understanding of the key mechanisms orchestrating fibroblast hyperactivity may help developing innovative therapeutic options to restrain myocardial or tumor stiffness and improve patient prognosis. Albeit still unappreciated, the dynamic transition of myocardial and tumor fibroblasts into myoFbs and CAFs shares several common triggers and signaling pathways relevant to TGF-β dependent cascade, metabolic reprogramming, mechanotransduction, secretory properties, and epigenetic regulation, which might lay the foundation for future antifibrotic intervention. Therefore, the aim of this review is to highlight emerging analogies in the molecular signature underlying myoFbs and CAFs activation with the purpose of identifying novel prognostic/diagnostic biomarkers, and to elucidate the potential of drug repositioning strategies to mitigate cardiac/cancer fibrosis.Copyright © 2023. Published by Elsevier Inc.