Journal article
Oncogenic Activity of Solute Carrier Family 45 Member 2 and Alpha-Methylacyl-Coenzyme A Racemase Gene Fusion Is Mediated by Mitogen-Activated Protein Kinase
Hepatology communications, Vol.6(1), pp.209-222
09/10/2021
DOI: 10.1002/hep4.1724
PMCID: PMC8710797
PMID: 34505419
Abstract
Chromosome rearrangement is one of the hallmarks of human malignancies. Gene fusion is one of the consequences of chromosome rearrangements. In this report, we show that gene fusion between solute carrier family 45 member 2 (SLC45A2) and alpha-methylacyl-coenzyme A racemase (AMACR) occurs in eight different types of human malignancies, with frequencies ranging from 45% to 97%. The chimeric protein is translocated to the lysosomal membrane and activates the extracellular signal-regulated kinase signaling cascade. The fusion protein promotes cell growth, accelerates migration, resists serum starvation-induced cell death, and is essential for cancer growth in mouse xenograft cancer models. Introduction of SLC45A2-AMACR into the mouse liver using a sleeping beauty transposon system and somatic knockout of phosphatase and TENsin homolog (Pten) generated spontaneous liver cancers within a short period. Conclusion: The gene fusion between SLC45A2 and AMACR may be a driving event for human liver cancer development.
Details
- Title: Subtitle
- Oncogenic Activity of Solute Carrier Family 45 Member 2 and Alpha-Methylacyl-Coenzyme A Racemase Gene Fusion Is Mediated by Mitogen-Activated Protein Kinase
- Creators
- Jun Zhang - University of IowaZe-Hua Zuo - University of Pittsburgh School of MedicineYan-Ping Yu - University of Pittsburgh School of MedicineDeqin Ma - University of IowaBao-Guo Ren - University of Pittsburgh School of MedicineSilvia Liu - University of PittsburghJoel Nelson - University of PittsburghZhou Wang - University of PittsburghJunyan Tao - University of PittsburghTirthadipa Pradhan-Sundd - University of Pittsburgh School of MedicineRohit Bhargava - University of PittsburghGeorge Michalopoulos - University of PittsburghQi Chen - University of KansasArjun Pennathur - University of PittsburghJames Luketich - University of PittsburghPaul Satdarshan Monga - University of Pittsburgh School of MedicineMichael Nalesnik - University of PittsburghJian-Hua Luo - University of Pittsburgh School of Medicine
- Resource Type
- Journal article
- Publication Details
- Hepatology communications, Vol.6(1), pp.209-222
- DOI
- 10.1002/hep4.1724
- PMID
- 34505419
- PMCID
- PMC8710797
- eISSN
- 2471-254X
- Grant note
- award: W81XWH‐16‐1‐0541; award: 1R56CA229262‐01;
- Language
- English
- Date published
- 09/10/2021
- Academic Unit
- Pathology; Internal Medicine
- Record Identifier
- 9984186560202771
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