2. Academic Validation
  3. Downregulation of 4-HNE and FOXO4 collaboratively promotes NSCLC cell migration and tumor growth

Downregulation of 4-HNE and FOXO4 collaboratively promotes NSCLC cell migration and tumor growth

  • Cell Death Dis. 2024 Jul 31;15(7):546. doi: 10.1038/s41419-024-06948-4.
Tianfei Zhong # 1 2,  Ying Li # 3,  Meng Jin # 3,  Jingqun Liu 3,  Zhenyu Wu 1 4,  Feiye Zhu 5,  Lisha Zhao 6,  Yongsheng Fan 4 7,  Li Xu 8 9,  Jinjun Ji 10 11
Affiliations

Affiliations

  • 1 College of Basic Medical, Zhejiang Chinese Medical University, Hangzhou, China.
  • 2 Logistic Affairs Department, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3 The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
  • 4 Key Laborat Laboratory of Chinese Medicine Rtheumatology of Zhejiang Province, Hangzhou, China.
  • 5 Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
  • 6 Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China.
  • 7 Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
  • 8 College of Basic Medical, Zhejiang Chinese Medical University, Hangzhou, China. xulihhb@163.com.
  • 9 Key Laborat Laboratory of Chinese Medicine Rtheumatology of Zhejiang Province, Hangzhou, China. xulihhb@163.com.
  • 10 College of Basic Medical, Zhejiang Chinese Medical University, Hangzhou, China. jijinjun@zcmu.edu.cn.
  • 11 Key Laborat Laboratory of Chinese Medicine Rtheumatology of Zhejiang Province, Hangzhou, China. jijinjun@zcmu.edu.cn.
  • # Contributed equally.
PMID: 39085238 DOI: 10.1038/s41419-024-06948-4
Abstract

Non-small cell lung Cancer (NSCLC) is among the most prevalent cancers and a leading cause of cancer-related mortality globally. Extracellular vesicles (EVs) derived from NSCLC play a pivotal role in lung Cancer progression. Our findings reveal a direct correlation between the abundance of EVs and the transfection efficiencies. Co-culturing two different lung Cancer cell lines could enhance EVs formation, cell proliferation, migration and tumorigenicity. mRNA chip and metabolic analyses revealed significant alterations in the FOXO signaling pathway and unsaturated fatty acid metabolism within tumor tissues derived from co-cultured cells. Shotgun lipidomics studies and bioinformatics analyses guided our attention towards 4-Hydroxynonenal (4-HNE) and FOXO4. Elevating 4-HNE or FOXO4 levels could reduce the formation of EVs and impede cell growth and migration. While silencing FOXO4 expression lead to an increase in cell cloning rate and enhanced migration. These findings suggest that regulating the production of 4-HNE and FOXO4 might provide an effective therapeutic approach for the treatment of NSCLC.

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