Protein kinase C a is involved in the regulation of AXL receptor tyrosine kinase expression in triple-negative breast cancer cells.

Molecular medicine reports

PubMedID: 27357025

Yue CH, Liu LC, Kao ES, Lin H, Hsu LS, Hsu CW, Lin YY, Lin YS, Liu JY, Lee CJ. Protein kinase C a is involved in the regulation of AXL receptor tyrosine kinase expression in triple-negative breast cancer cells. Mol Med Rep. 2016;.
AXL receptor tyrosine kinase is overexpressed in triple-negative breast cancer (TNBC), and has a function in cancer progression and metastases. However, the mechanism underlying AXL gene regulation in TNBC remains unknown. In this study, the involvement of protein kinase C a (PKCa) in the expression of AXL was investigated in human TNBC cells. The microarray data from other studies showed that PKCa is significantly correlated with AXL expression in TNBC cell lines. Tissue array analysis also confirmed their correlation in TNBC. The PKCa inhibitor Go6976 was used to treat MDA-MB-231 and Hs578T TNBC cells, which resulted in decreased expression of AXL and epithelia-mesenchymal transition-related gene vimentin, and decreased cell proliferation. An MZF-1 acidic domain fragment (MZF-1 peptide), which was designed to downregulate PKCa expression, was transfected into the cells and resulted in inhibition of AXL expression. This effect was reversed by co-treatment with the constitutive form of PKCa. Moreover, the downregulation of PKCa was also confirmed by treatment with TAT-fused MZF-1 peptide. Thus, the current study proposes that AXL may be correlated with PKCa-dependent TNBC cells, and could be modulated by MZF-1 peptides.