2. Academic Validation
  3. IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis

IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis

  • Cell Death Differ. 2022 Aug;29(8):1528-1540. doi: 10.1038/s41418-022-00940-1.
Wei Xie  # 1 2,  Qiwei Jiang  # 2,  Xueji Wu  # 2,  Lei Wang  # 2,  Bing Gao 2,  Zicheng Sun 1,  Xiaomei Zhang 2,  Lang Bu 2,  Ying Lin 1,  Qiang Huang 3,  Jie Li 4,  Jianping Guo 5
Affiliations

Affiliations

  • 1 Department of Breast and Thyroid Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China.
  • 2 Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China.
  • 3 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China. huangqiang209@163.com.
  • 4 Department of Breast and Thyroid Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China. Lijie78@mail.sysu.edu.cn.
  • 5 Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China. guojp6@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 35066576 DOI: 10.1038/s41418-022-00940-1
Abstract

IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast Cancer. However, the potential function and underlying mechanism of IKBKE contributing to breast Cancer metastasis remain largely elusive. Here, we report that depletion of Ikbke markedly decreases polyoma virus middle T antigen (PyVMT)-induced mouse mammary tumorigenesis and subsequent lung metastasis. Biologically, ectopic expression of IKBKE accelerates, whereas depletion of IKBKE attenuates breast Cancer invasiveness and migration in vitro and tumor metastasis in vivo. Mechanistically, IKBKE tightly controls the stability of transcriptional factor Snail in different layers, in particular by directly phosphorylating Snail, which markedly blocks the E3 ligase β-TRCP1-mediated Snail degradation, resulting in breast Cancer epithelial-mesenchymal transition (EMT) and metastasis. These findings together reveal a novel oncogenic function of IKBKE in promoting breast Cancer metastasis by governing Snail abundance, and highlight the potential of targeting IKBKE for metastatic breast Cancer therapies.

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