FAXC interacts with ANXA2 and SRC in mitochondria and promotes tumorigenesis in cholangiocarcinoma.
Haruna FujimoriMao Shima-NakamuraShin-Ichiro KannoRie Shibuya-TakahashiMai MochizukiMasamichi MizumaMichiaki UnnoYuta WakuiMakoto AbueWataru IwaiDaisuke FukushiKennich SatohKazunori YamaguchiNorihisa ShindoJun YasudaKeiichi TamaiPublished in: Cancer science (2024)
Cholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c-SRC, which are tumor-promoting genes. The FAXC/ANXA2/c-SRC complex forms in the mitochondria. FAXC enhances SRC-dependent ANXA2 phosphorylation at tyrosine-24, and the C-terminal amino acid residues (351-375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial-mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets.
Keyphrases
- tyrosine kinase
- genome wide
- epithelial mesenchymal transition
- bioinformatics analysis
- genome wide identification
- amino acid
- cell death
- single cell
- gene expression
- dna methylation
- reactive oxygen species
- genome wide analysis
- signaling pathway
- transforming growth factor
- endoplasmic reticulum
- type diabetes
- rna seq
- adipose tissue
- high fat diet induced
- optical coherence tomography
- transcription factor