1. Academic Validation
  2. Centromere protein I facilitates breast cancer tumorigenesis and disease progression through modulation of Wnt/β-Catenin signaling

Centromere protein I facilitates breast cancer tumorigenesis and disease progression through modulation of Wnt/β-Catenin signaling

  • Cancer Cell Int. 2025 Oct 10;25(1):348. doi: 10.1186/s12935-025-04001-8.
Chaoshen Wu # 1 Yibing Zhou # 1 Yuxiao Mu # 2 Yijie Cheng 3 Wenqian Xu 4 Mengna Huang 1 Jingyuan Xu 5 Ming Li 6 Jianfeng Gu 7 Xuli Meng 8 Da Qian 9
Affiliations

Affiliations

  • 1 Central Laboratory, Department of Scientific Research, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, 215500, Changshu, Suzhou, Jiangsu Province, China.
  • 2 General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China.
  • 3 Department of Pharmacy, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, 215500, Changshu, Suzhou, Jiangsu Province, China.
  • 4 Department of Thyroid and Breast Surgery, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, 215500, Changshu, Suzhou, Jiangsu Province, China.
  • 5 School of Biology and Food Engineering, Suzhou University of Technology, 215500, Changshu, Suzhou, Jiangsu Province, China.
  • 6 Department of General Surgery, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, 215500, Changshu, Suzhou, Jiangsu Province, China.
  • 7 Department of General Surgery, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, 215500, Changshu, Suzhou, Jiangsu Province, China. jscsgjf@sina.cn.
  • 8 General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China. mxlmail@126.com.
  • 9 Central Laboratory, Department of Scientific Research, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, 215500, Changshu, Suzhou, Jiangsu Province, China. qianda0215@suda.edu.cn.
  • # Contributed equally.
Abstract

Background: Breast Cancer (BCa) is a major contributor to female mortality worldwide. Treatment resistance and tumor heterogeneity contribute to the lack of effective therapeutic targets, posing a significant challenge in BCa management. CENPI, a core centromere protein involved in chromosome segregation, has emerging evidence implicating it in oncogenesis across diverse malignancies. However, its functional and molecular mechanisms in BCa remain unclear.

Methods: We analyzed CENPI expression and its clinical significance by using the BCa dataset from the Cancer Genome Atlas (TCGA) and immunohistochemical staining of 3 human BCa tissue samples. Cellular functional assays and mice xenograft models were utilized to assess the effects of CENPI on BCa growth. RNA Sequencing combined with bioinformatics analysis was conducted to elucidate the molecular mechanisms underlying CENPI function, with further validation through Western blotting, immunofluorescence, and TOP/FOP flash assays.

Results: CENPI was aberrantly overexpressed in BCa, with elevated expression levels strongly associated with disease progression and poor prognosis. Functional assays demonstrated that CENPI significantly promoted breast carcinogenesis in both cellular and animal models. Mechanistically, CENPI increased BCa progression and malignant phenotypes by modulating the Wnt/β-catenin axis.

Conclusions: CENPI is a critical oncogene in BCa, driving tumorigenesis and disease progression via the Wnt/β-catenin axis, which represents a promising biomarker and therapeutic target for BCa.

Keywords

Breast cancer; CENPI; Chromosome; Mitosis; Wnt/β-catenin signaling.

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