Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c‐MYC axis in breast cancer. Issue 3 (16th January 2020)

• Record Type: Journal Article
• Authors: Liu, Yan; Song, Hang; Yu, Shiyi; Huang, Kuo‐Hsiang; Ma, Xinxing; Zhou, Yehui; Yu, Shuang; Zhang, Jingzhong; Chen, Liming
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 3(2020)
• Page Start: 2135
• Page End: 2144
• Publication Date: 2020-01-16
• Subjects: breast cancer -- c‐MYC -- ERK1 -- Protein Kinase D3; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.14772
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Breast cancer is the second leading death cause of cancer death for all women. Previous study suggested that Protein Kinase D3 (PRKD3) was involved in breast cancer progression. In addition, the protein level of PRKD3 in triple‐negative breast adenocarcinoma was higher than that in normal breast tissue. However, the oncogenic mechanisms of PRKD3 in breast cancer is not fully investigated. Multi‐omic data showed that ERK1/c‐MYC axis was identified as a major pivot in PRKD3‐mediated downstream pathways. Our study provided the evidence to support that the PRKD3/ERK1/c‐MYC pathway play an important role in breast cancer progression. We found that knocking out PRKD3 by performing CRISPR/Cas9 genome engineering technology suppressed phosphorylation of both ERK1 and c‐MYC but did not down‐regulate ERK1/2 expression or phosphorylation of ERK2. The inhibition of ERK1 and c‐MYC phosphorylation further led to the lower protein level of c‐MYC and then reduced the expression of the c‐MYC target genes in breast cancer cells. We also found that loss of PRKD3 reduced the rate of the cell proliferation in vitro and tumour growth in vivo, whereas ectopic (over)expression of PRKD3, ERK1 or c‐MYC in the PRKD3‐knockout breast cells reverse the suppression of the cell proliferation and tumour growth. Collectively, our data strongly suggested that PRKD3 likely promote the cell proliferation in the breast cancer cells by activating ERK1‐c‐MYC axis.