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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Breast Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1591706

This article is part of the Research TopicAI-Powered Insights: Predicting Treatment Response and Prognosis in Breast CancerView all 14 articles

CDK1 May Promote Breast Cancer Progression through AKT Activation and Immune Modulation

Provisionally accepted
Huanhong  ZengHuanhong Zeng1Minxue  ZhuangMinxue Zhuang1Bochuan  LiangBochuan Liang2Feili  CaiFeili Cai1Mengbo  LinMengbo Lin1Huan  WangHuan Wang3Ruo  WangRuo Wang1*Hui  ZhangHui Zhang1
  • 1Department of Breast Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
  • 2Nanchang Medical College, Nanchang, Jiangxi Province, China
  • 3Jiaxing Maternity and Child Health Care Hospital, Jiaxing, Zhejiang, China

The final, formatted version of the article will be published soon.

Background: Cyclin-dependent kinase 1 (CDK1) plays a crucial role in regulating the cell cycle, yet its clinical relevance and molecular mechanisms in breast cancer remain insufficiently characterized. This study aimed to comprehensively evaluate CDK1 expression, prognostic value, and biological functions in breast cancer through integrated bioinformatics and experimental analyses. Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) were analyzed to assess CDK1 expression, diagnostic efficacy, and survival associations. Immune infiltration and tumor mutation burden (TMB) were evaluated using TIMER and CIBERSORT algorithms. Single-cell RNA sequencing data from TISCH2 were employed to examine cell-type-specific expression. Functional experiments, including shRNA-mediated CDK1 knockdown, Western blotting, and CCK-8 assays, were performed to validate its biological role in MDA-MB-231 cells. Results: CDK1 expression was elevated in breast cancer tissues compared with normal controls and exhibited high diagnostic accuracy (AUC = 0.978). Elevated CDK1 levels were associated with HER2-, ER-, and PR-negative subtypes and enriched in Basal-like breast cancer. Patients with high CDK1 expression showed poorer disease-specific survival (HR = 1.67, p = 0.024). Immune analysis revealed positive correlations between CDK1 and immune cell infiltration, particularly CD4+ memory T cells, CD8+ T cells, etc. as well as a moderate association with TMB. Single-cell analysis indicated that CDK1 was preferentially expressed in CD8+ T cells and M1 macrophages. Mechanistically, CDK1 knockdown reduced AKT phosphorylation and downregulated Cyclin D1, A, and E1, leading to suppressed proliferation of breast cancer cells. Conclusion: CDK1 acts as a multifaceted oncogenic factor in breast cancer, contributing to tumor growth and immune modulation. Its overexpression is linked to poor prognosis and enhanced immune infiltration, underscoring its potential as a diagnostic and therapeutic target. Targeting CDK1 or its downstream signaling pathways may offer novel strategies, particularly for aggressive subtypes such as Basal-like or triple-negative breast cancer.

Keywords: Cdk1, breast cancer, AKT signaling, Immune infiltration, prognosis, biomarker

Received: 11 Mar 2025; Accepted: 20 Oct 2025.

Copyright: © 2025 Zeng, Zhuang, Liang, Cai, Lin, Wang, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ruo Wang, wangruo@sjtu.edu.cn

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