Abstract

We have previously identified a novel Aurora-A-mediated Serine 379 (S379) phosphorylation of a poly(C)-binding protein, hnRNPK, the overexpression of which is frequently observed in various cancers. It is known that the oncogenic Aurora-A kinase promotes the malignancy of cancer cells. This study aims to investigate the unexplored functions of hnRNPK S379 phosphorylation using MDA-MB-231 cells, a triple negative breast cancer cell that has amplification of the Aurora-A kinase gene. Accordingly, we established two cell lines in which the endogenous hnRNPK was replaced with either S379D or S379A hnRNPK respectively. Notably, we found that a phosphorylation-mimic S379D mutant of hnRNPK suppressed cell migration and, conversely, a phosphorylation-defective S379A mutant promoted migration. Moreover, Twist was downregulated upon hnRNPK S379 phosphorylation, whereas β-catenin and MMP12 were increased when there was loss of hnRNPK S379 phosphorylation in MDA-MB-231 cells. Furthermore, S379A hnRNPK increases stability of β-catenin in MDA-MB-231 cells. In conclusion, our results suggest that hnRNPK S379 phosphorylation regulates migration via the EMT signaling pathway.

Details

Title
hnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells
Author
Hsin-Yu, Tsai 1 ; Shu-Ling, Fu 2 ; Ling-Ming, Tseng 3 ; Chiu Jen-Hwey 4 ; Chao-Hsiung, Lin 5 

 National Yang-Ming University, Department of Life Sciences and Institute of Genome Sciences, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914) 
 National Yang-Ming University, Institute of Traditional Medicine, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914) 
 Taipei Veterans General Hospital, Comprehensive Breast Health Center, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314) 
 National Yang-Ming University, Institute of Traditional Medicine, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914); Taipei Veterans General Hospital, Comprehensive Breast Health Center, Taipei, Taiwan (GRID:grid.278247.c) (ISNI:0000 0004 0604 5314) 
 National Yang-Ming University, Department of Life Sciences and Institute of Genome Sciences, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914); National Yang-Ming University, Institute of Biopharmaceutical Sciences, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914); National Yang-Ming University, Proteomics Research Center, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914); National Yang-Ming University, Aging and Health Research Center, Taipei, Taiwan (GRID:grid.260770.4) (ISNI:0000 0001 0425 5914) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2227829595
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.