Oncogenic Activity of Solute Carrier Family 45 Member 2 and Alpha‐Methylacyl‐Coenzyme A Racemase Gene Fusion Is Mediated by Mitogen‐Activated Protein Kinase
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 10, 2021
- Source ID
- 10.1002/hep4.1724
Entities
People
- Arjun Pennathur
- Bao‐guo Ren
- Deqin Ma
- George Michalopoulos
- James Luketich
- Jian‐hua Luo
- Joel Nelson
- Jun Zhang
- Junyan Tao
- Michael Nalesnik
- Paul Satdarshan Monga
- Qi Chen
- Rohit Bhargava
- Silvia Liu
- Tirthadipa Pradhan‐Sundd
- Yan‐ping Yu
- Ze‐hua Zuo
- Zhou Wang
Organizations
- University of Iowa
- University of Kansas
- University of Pittsburgh