Aurora kinases are essential for PKC-induced invasion and matrix metalloproteinase-9 expression in MCF-7 breast cancer cells

Abstract

The Aurora kinase family of serine/threonine kinases are known to be crucial for cell cycle control. Aurora kinases are considered a target of anticancer drugs. However, few studies have assessed the effect of Aurora kinases in breast cancer. In the present study, to determine whether Aurora kinases play a role in oncogenic actions of protein kinase C (PKC), we investigated the effect of Aurora kinases on PKC-induced invasion and MMP-9 expression using breast cancer cells. Treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the upregulation and phosphorylation of Aurora kinases via the MAPK signaling pathway. Moreover, the inhibition of Aurora kinases by their siRNAs and inhibitors suppressed TPA-induced cell invasion and expression of MMP-9 by inhibiting the activation of NF-κB/AP-1, major transcription factors for MMP-9 expression in MCF-7 cells. These results suggested that Aurora kinases mediate PKC-MAPK signal to NF-κB/AP-1 with increasing MMP-9 expression and invasion of MCF-7 cells. To the best of our knowledge, this is the first study to show that Aurora kinases are key molecules in PKC-induced invasion in breast cancer cells.

Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells

“…The invasion ( 35 ) and migration assays ( 37 ) were performed as previously described. Cell growth medium (0.5 ml) with cells was added to the upper chamber, and medium with TPA alone or with SME was added to bottom wells.…”

Aurora kinases: novel therapy targets in cancers

“…Also, other constitutive activation of oncogenic signalings, such as Raf-1 [80], Myc [81], OCT4 [82], promote the EMT progression via the stabilization and accumulation of AURKA. In addition, AURKA overexpression can significantly enhance the expression of matrix metalloproteinases (MMP)-2, MMP-7 and MMP-10, leading to degradation of extracellular matrix proteins, which stimulates tumor cell mobility and metastasis [20, 83]. …”

The dual mTOR kinase inhibitor TAK228 inhibits tumorigenicity and enhances radiosensitization in diffuse intrinsic pontine glioma

“…Invasion is also regulated by both mTORC1 and mTORC2 [45; 46; 47; 48; 49]. TAK228 treatment at 10 nM decreased invading cells in a Boyden matrigel transwell chamber assay by approximately 80% compared to DMSO in both SU-DIPG-XIII and JHH DIPG1 (p<0.0001 vs DMSO control) (Fig.…”

“…Meanwhile, multiple pro-invasion genes downstream of mTORC1 and mTORC2 are associated with metastasis in breast cancer [46; 48; 49], hepatocellular carcinoma [45; 52], and melanoma [47]. Furthermore, mTORC2, like mTORC1, is known to regulate cell growth through MYC activation [53].…”