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HnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells.

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.

SUBMITTER: Tsai HY

PROVIDER: S-EPMC6527834 | biostudies-other | 2019 May

REPOSITORIES: biostudies-other

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hnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells.

Tsai Hsin-Yu HY Fu Shu-Ling SL Tseng Ling-Ming LM Chiu Jen-Hwey JH Lin Chao-Hsiung CH

Scientific reports 20190520 1

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, ...[more]

PMID: 31110205

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Project description:Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.

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HnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells.

Publications

hnRNPK S379 phosphorylation participates in migration regulation of triple negative MDA-MB-231 cells.

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