Author:
Qian Jun,Hassanein Mohamed,Hoeksema Megan D.,Harris Bradford K.,Zou Yong,Chen Heidi,Lu Pengcheng,Eisenberg Rosana,Wang Jing,Espinosa Allan,Ji Xiangming,Harris Fredrick T.,Rahman S. M. Jamshedur,Massion Pierre P.
Abstract
Aberrant expression of RNA-binding proteins has profound implications for cellular physiology and the pathogenesis of human diseases such as cancer. We previously identified the Fragile X-Related 1 gene (FXR1) as one amplified candidate driver gene at 3q26-29 in lung squamous cell carcinoma (SCC). FXR1 is an autosomal paralog of Fragile X mental retardation 1 and has not been directly linked to human cancers. Here we demonstrate that FXR1 is a key regulator of tumor progression and its overexpression is critical for nonsmall cell lung cancer (NSCLC) cell growth in vitro and in vivo. We identified the mechanisms by which FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota and epithelial cell transforming 2, located in the same amplicon via distinct binding mechanisms. FXR1 expression is a candidate biomarker predictive of poor survival in multiple solid tumors including NSCLCs. Because FXR1 is overexpressed and associated with poor clinical outcomes in multiple cancers, these results have implications for other solid malignancies.
Funder
HHS | NIH | National Cancer Institute
DOD | Congressionally Directed Medical Research Programs
Publisher
Proceedings of the National Academy of Sciences
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