journal article·2025-04Open access

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

Yu Tang, Rui Liu, Jing Zhu, Qian He, Chenglong Pan, Zhongmei Zhou, Jian Sun, Fubing Li, Longlong Zhang, Yujie Shi, Jing Yao, Dewei Jiang, Ceshi Chen

Advanced Science· Volume 12· Issue 16

Abstract

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.
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Research context

OpenAlex topics: Kruppel-like factors research · Nuclear Structure and Function · Cancer-related Molecular Pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

Yunnan Key Laboratory of Breast Cancer Precision Medicine Institute of Biomedical Engineering Kunming Medical University Kunming 650000 China

Department of Pathology The First Affiliated Hospital of Kunming Medical University Kunming 650032 China

School of Continuing Education Kunming Medical University Kunming 650021 China

Department of Pathology Henan Provincial People's Hospital Zhengzhou University Zhengzhou 450003 China

Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Institute of Radiation Oncology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650201 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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