Centromere protein U (CENPU) enhances angiogenesis in triple-negative breast cancer by inhibiting ubiquitin–proteasomal degradation of COX-2
Authors: Jingjing Liu
Zhendong Shi
Yufan Qiu
Qianxi Yang
Jin Zhang
Lixia Cao
Teng Pan
Guanglin Zhou
Dongdong Zhou
Journal: Cancer Letters (2020)
Discipline: CLINICAL MEDICINE
Keywords: Angiogenesis; CENPU; COX-2; TNBC; VEGFA.
Affiliations: 3rd Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China; Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education, Tianjin, PR China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China; Tianjin's Clinical Research Center for Cancer, Tianjin, PR China; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, PR China., 3rd Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China., 3rd Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China; Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education, Tianjin, PR China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, PR China; Tianjin's Clinical Research Center for Cancer, Tianjin, PR China; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, PR China. Electronic address: .

Abstract:  Triple-negative breast cancer (TNBC) is characterized by high vascularity, but anti-angiogenic therapies show poor efficacy. Centromere protein U (CENPU), a centromere component essential for mitosis, is associated with tumorigenesis in multiple cancers; however, little is known of its role in breast cancer. Here, we investigate its expression and function of promoting angiogenesis in TNBC. Immunohistochemical staining revealed high CENPU expression in TNBC tissue and high CENPU levels correlated significantly with poor distant metastasis-free and overall survival. Knockdown of CENPU in TNBC cells inhibited vascular endothelial growth factor A (VEGFA) production and significantly reduced tube formation and migration of human umbilical vein endothelial cells in vitro. In a mouse xenograft model, CENPU knockdown reduced TNBC tumor growth concomitant with a reduction in CD31 + microvessel density. Mechanistic studies revealed that CENPU promoted angiogenesis by inhibiting the ubiquitination and proteasomal degradation of cyclooxygenase-2 (COX-2), leading to increased activation of the COX-2-p-ERK-HIF-1α-VEGFA signaling pathway. Taken together, our results demonstrate a critical role for CENPU in COX-2-mediated signaling for angiogenesis, and identify a role of CENPU in regulating angiogenesis in TNBC. 

Retracted: No

PubPeer comments:
 A number of the images in Figure 2a seem to have repeated areas, as if they were cut and pasted. Orange  X indicates an area that isn t identical. Could the authors please comment? *** ![file] , 
 March 8, 2022 from journal via email:  Thank you again for flagging up concerns relating to [this article] published in Cell Bioscience. The Editors have carefully assessed the images in question and do not see any need for concern or correction. The patterns within the tissue were similar, which is not necessarily due to manipulation. , 
 The Editors might want to reconsider their  careful assessment . Here are some additional findings. ![file] ,