线粒体功能障碍的癌细胞可以被肿瘤微环境中的细胞拯救。使用人腺样囊性癌细胞系和成纤维细胞，我们发现线粒体转移不仅发生在人类细胞之间，而且发生在体外和体内的人和小鼠细胞之间。有趣的是，癌细胞和成纤维细胞之间也可能出现自发的细胞融合。特定的染色体丢失可能对于细胞核重组和杂交后选择过程至关重要。通过隧道纳米管（TNT）的线粒体转移和细胞融合都“选择性地”复活癌细胞，而线粒体功能障碍是关键诱因。除了线粒体转移之外，细胞融合还能显着增强癌症的恶性程度并促进上皮间质转化。从机制上讲，癌细胞中的线粒体功能障碍导致 L-乳酸分泌，吸引成纤维细胞延长 TNT 和 TMEM16F 介导的磷脂酰丝氨酸外化，促进 TNT 形成和细胞膜融合。我们的研究结果提供了对线粒体转移和细胞融合的见解，突出了潜在的癌症治疗目标。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion "selectively" revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.