Hypo‐phosphorylated hnRNPK promotes migration of triple negative breast cancer cells through an Aurora‐A‐independent manner

HnRNPK, a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family, is well known as a poly(C)‐binding protein that participates in RNA processing and translational regulations. Importance of hnRNPK in tumorigenesis has been implicated by its persistent amplification in a wide range of cancers, whereas diverse post‐transcriptional modifications (PTMs) of hnRNPK also have been shown to regulate its protein function. We previously reported a novel Aurora‐A‐mediated phosphorylation of hnRNPK, but the cellular function of such phosphorylation remains unknown. Because Aurora‐A has been known as an oncogenic kinase and promotes transformation, growth and migration of cancer cells, we further investigated the functional role of hnRNPK phosphorylation in MDA‐MB‐231 cell line, a triple negative breast cancer cell with amplification of Aurora‐A. Accordingly, two stable clones replacing endogenous hnRNPK with either phosphorylation‐defective or phosphorylation‐mimic mutants were established, namely MDA‐MB‐231‐SA and MDA‐MB‐231‐SD. To determine whether such hnRNPK phosphorylation participates in the Aurora‐A‐mediated migration signaling, migration ability was compared between the hnRNPK phosphorylation‐defective and phosphorylation‐enhancing cells. Our results showed that migration ability of MDA‐MB‐231‐SA cells is higher than the control MDA‐MB‐231 cells but migration ability of MDA‐MB‐231‐SD cells is less than control, suggesting that Aurora‐A‐mediated hnRNPK phosphorylation does not promote cell migration but instead suppresses it, likely through an Aurora‐A‐independent manner. Therefore, it is proposed that such hnRNPK phosphorylation is not only mediated by Aurora‐A amplification but also regulated by other factors. It has been shown that different PTMs of hnRNPK are able to crosstalk with each other, and synergistically influence protein functions. My data showed that such Aurora‐A‐mediated phosphorylation was inhibited by arginine methylation of hnRNPK, whereas cell migration was decreased upon deficiency of hnRNPK arginine methylation in MDA‐MB‐231 cells. Further verification of migration‐associated signaling pathway showed that levels of EMT‐related proteins, Twist and β‐catenin, and RNA levels of MMP family were increased in MDA‐MB‐231‐SA cells. In conclusion, our results imply that a hypo‐phosphorylated status of hnRNPK may promote cell migration through hnRNPK‐β‐catenin‐MMP pathway. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .