1. Academic Validation
  2. Deciphering the performance of polo-like kinase 1 in triple-negative breast cancer progression according to the centromere protein U-phosphorylation pathway

Deciphering the performance of polo-like kinase 1 in triple-negative breast cancer progression according to the centromere protein U-phosphorylation pathway

  • Am J Cancer Res. 2021 May 15;11(5):2142-2158.
Shaorong Zhao 1 2 3 4 Yannan Geng 5 Lixia Cao 1 2 3 4 Qianxi Yang 1 2 3 4 Teng Pan 1 2 3 4 Dongdong Zhou 1 2 3 4 Jingjing Liu 1 2 3 4 Zhendong Shi 1 2 3 4 Jin Zhang 1 2 3 4
Affiliations

Affiliations

  • 1 The 3rd Department of Breast Cancer, Treatment and Research Center, China Tianjin Breast Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin 300060, People's Republic of China.
  • 2 Key Laboratory of Cancer Prevention and Therapy Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin 300060, People's Republic of China.
  • 3 Tianjin's Clinical Research Center for Cancer Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin 300060, People's Republic of China.
  • 4 Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin 300060, People's Republic of China.
  • 5 Department of Spinal Surgery, Tianjin Union Medical Center Hongqiao District, Tianjin 300121, People's Republic of China.
PMID: 34094674
Abstract

In general, the lack of effective therapeutic targets has led to the poor prognosis of triple-negative breast Cancer (TNBC). Polo-like kinase 1 (PLK1) has been studied extensively as an effective therapeutic objective for the progression of tumor. Although the fundamental strategy and function of PLK1 in TNBC are still unclear. Here, we demonstrated that PLK1 upregulation was significantly correlated with poor prognosis in breast Cancer cases utilizing the TCGA database. Additionally, ectopic PLK1 expression promoted TNBC cell proliferation, VEGFA production, and endothelial cell tube formation, whereas PLK1 knockdown induced the opposite effects. Moreover, expression of PLK1 K82R, the kinase-dead mutant of PLK1, completely inhibited PLK1-mediated cell proliferation, VEGFA production, and tube formation. Gene Set Enrichment Analysis (GSEA) showed that PLK1 expression significantly correlated with mitosis and the VEGF signaling pathway. We further observed that PLK1 phosphorylated centromere protein U (CENPU) at residue T78, thereby regulating the signaling pathway of COX-2/HIF-1α/VEGFA and the metaphase-anaphase transition of mitosis. The mechanism underlying the activity of PLK1 was also determined using a TNBC xenograft mouse model. Moreover, a PLK1 Inhibitor effectively inhibited TNBC progression. Taken together, our results revealed that PLK1 plays an important role in TNBC progression via its kinase activity and phosphorylation of CENPU. Thus, PLK1 is an effective therapeutic objective for TNBC.

Keywords

Angiogenesis; CENPU; PLK1; TNBC; cell proliferation.

Figures
Products