2. Academic Validation
  3. Beyond mitochondrial transfer, cell fusion rescues metabolic dysfunction and boosts malignancy in adenoid cystic carcinoma

Beyond mitochondrial transfer, cell fusion rescues metabolic dysfunction and boosts malignancy in adenoid cystic carcinoma

  • Cell Rep. 2024 Sep 24;43(9):114652. doi: 10.1016/j.celrep.2024.114652.
Xianghe Qiao 1,  Nengwen Huang 2,  Wanrong Meng 2,  Yunkun Liu 2,  Jinjin Li 1,  Chunjie Li 2,  Wenxuan Wang 2,  Yi Lai 3,  Yongjiang Zhao 4,  Zhongkai Ma 2,  Jingya Li 2,  Xuan Zhang 3,  Zhijie Weng 2,  Chenzhou Wu 2,  Longjiang Li 5,  Bo Li 6
Affiliations

Affiliations

  • 1 Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
  • 2 Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
  • 3 Department of Medical Genetics/Prenatal Diagnostic Center, West China Second Hospital, Sichuan University, Chengdu 610041, China.
  • 4 Genetics and Prenatal Diagnostic Center, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Zhengzhou 450052, China.
  • 5 Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: muzili63@163.com.
  • 6 State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: libo.scu@foxmail.com.
PMID: 39217612 DOI: 10.1016/j.celrep.2024.114652
Abstract

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.

Keywords

CP: Cancer; CP: Cell biology; adenoid cystic carcinoma; cell fusion; fibroblasts; mitochondrial dysfunction; mitochondrial transfer.

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