Oncotarget

Research Papers:

Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells

Elizabeth T. Chang _, Palak R. Parekh, Qingyuan Yang, Duc M. Nguyen and France Carrier

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:10578-10593. https://doi.org/10.18632/oncotarget.7020

Metrics: PDF 863 views  |   HTML 1254 views  |   ?  


Abstract

Elizabeth T. Chang1, Palak R. Parekh1, Qingyuan Yang1, Duc M. Nguyen1, France Carrier1

1Marlene and Stewart Greenebaum Cancer Center, School of Medicine, Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA

Correspondence to:

France Carrier, e-mail: fcarrier@som.umaryland.edu

Keywords: cancer, hnRNP A18, hypoxia, protein translation, RNA-binding protein

Received: August 02, 2015     Accepted: January 13, 2016     Published: January 25, 2016

ABSTRACT

The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3’UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1α and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 7020