Oncogenic Activity of Solute Carrier Family 45 Member 2 and Alpha‐Methylacyl‐Coenzyme A Racemase Gene Fusion Is Mediated by Mitogen‐Activated Protein Kinase

Autor: Ze-Hua Zuo, Silvia Liu, Deqin Ma, Joel B. Nelson, James D. Luketich, Paul Satdarshan Monga, George K. Michalopoulos, Qi Chen, Jianhua Luo, Yanping Yu, Rohit Bhargava, Baoguo Ren, Arjun Pennathur, Michael A. Nalesnik, Jun Zhang, Junyan Tao, Tirthadipa Pradhan-Sundd, Zhou Wang
Rok vydání: 2021
Předmět:
Zdroj: Hepatology Communications, Vol 6, Iss 1, Pp 209-222 (2022)
Hepatology Communications
ISSN: 2471-254X
DOI: 10.1002/hep4.1724
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: