2. Academic Validation
  3. Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer

Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer

  • Adv Sci (Weinh). 2025 Jan 30:e2412096. doi: 10.1002/advs.202412096.
Yu Tang 1,  Rui Liu 1,  Jing Zhu 2,  Qian He 2,  Chenglong Pan 3,  Zhongmei Zhou 4,  Jian Sun 1,  Fubing Li 2,  Longlong Zhang 2,  Yujie Shi 5,  Jing Yao 6 7,  Dewei Jiang 8,  Ceshi Chen 1 2
Affiliations

Affiliations

  • 1 Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, 650118, China.
  • 2 Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650000, China.
  • 3 Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
  • 4 School of Continuing Education, Kunming Medical University, Kunming, 650021, China.
  • 5 Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, 450003, China.
  • 6 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 7 Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 8 Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China.
PMID: 39888288 DOI: 10.1002/advs.202412096
Abstract

Basal-like breast Cancer (BLBC), overlapping with the subgroup of Estrogen Receptor (ER), Progesterone Receptor (PR), and HER2 triple-negative breast Cancer, has the worst prognosis and limited therapeutics. The XPO1 gene encodes nuclear export protein 1, a promising Anticancer target which mediates nucleus-cytoplasm transport of nuclear export signal containing proteins such as tumor suppressor RB1 and some RNAs. Despite drugs targeting XPO1 are used in clinical, the regulation of XPO1 expression and functional mechanism is poorly understood, especially in BLBC. This study finds that KLF5 is a transcription factor of XPO1, which increases RB1 nuclear export and cell proliferation in BLBC cells. Furthermore, XPO1 interacts with the RNA-binding protein PTBP1 to export FOXO1 mRNA to cytoplasm and thus activates the FOXO1-KLF5 axis as a feedback. This work demonstrates that XPO1 inhibitor KPT-330 in combination with CDK4/6 inhibitor additively suppressed BLBC tumor growth in vivo. These results reveal a novel positive feedback regulation loop between KLF5 and XPO1 and provide a novel treatment strategy for BLBC.

Keywords

KLF5; RB1; XPO1; basal like breast cancer; cell cycle.

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