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Cited by 11Estrogen and related hormone effectsBreast Cancer Treatment StudiesMicroRNA in disease regulation

HGF/c‐Met Promotes Breast Cancer Tamoxifen Resistance Through the EZH2/HOTAIR‐miR‐141/200a Feedback Signaling Pathway

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Lai, Xiaofeng, Zhang, Yuan, Li, Mengyang, Yu, Shentong, Wang, Shuiliang, Zhang, Shenghang, Niu, Huimin, Chen, Li +3 more·2025·Molecular Carcinogenesis
DOI 10.1002/mc.23878
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Abstract

Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor‐positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c‐Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear. In our study, we found that the activation of HGF/c‐Met was crucial for TR maintenance. Synergistic interaction with HOTAIR and EZH2 accelerated HGF expression by repressing miR‐141/200a. Additionally, HGF/c‐Met activated NF‐κB, forming a positive feedback loop of EZH2/HOTAIR‐miR‐141/200a‐HGF/c‐Met‐NF‐κB. Our findings indicated that HGF/c‐Met functioned as an important biomarker for TR, and HGF/c‐Met inhibition provided a novel approach to TR treatment.

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  • Approximately 30% of ER+ breast cancer cases recur with resistance to Tamoxifen, and this recurrence can lead to more aggressive neoplasms.

    “Approximately 30% of ER+ breast cancer cases recur with resistance to Tamoxifen, and this recurrence can lead to more aggressive neoplasms23,24.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [23]

    The Introduction says approximately 30% of ER+ breast cancer patients have primary tamoxifen resistance, not that 30% recur with resistance. Section 3.1 reports that tamoxifen-resistant cells showed more aggressive biological functions than parental cells, but does not establish that recurrence leads to more aggressive tumors in patients. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Lai, X., Zhang, Y., Li, M., Yu, S., Wang, S., Zhang, S., Niu, H., Chen, L., Lan, X., Zhang, J., & Chen, S.
Affiliations
  • Fujian Medical University (CN)
  • Shaanxi Provincial People's Hospital (CN)
  • Chinese PLA General Hospital (CN)
  • Department of Pathology 900TH Hospital of Joint Logistics Support Force Fuzhou China
  • Air Force Medical University (CN)
  • Xijing Hospital (CN)
Corresponding author
  • Lan, Xiaopeng
  • Zhang, Jian
  • Chen, Suning
ORCID
Venue
Molecular Carcinogenesis
Publisher
Wiley
Published
2025-01-24
Volume
64
Issue
4
Pages
769-783
ISSN
  • 0899-1987 (ISSN-L)
  • 1098-2744
DOI
10.1002/mc.23878
OpenAlex
W4406807466
Cited by
11
References
1
Citations by year
2026: 4 · 2025: 7
FWCI
6.42
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Molecular Carcinogenesis (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (82073202, 81972710)
  • Natural Science Foundation of Fujian Province (2021J011269)
  • Chinese People’s Liberation Army
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
tamoxifen resistance, breast cancer, HGF/MET signaling, EZH2, HOTAIR, miR-141, miR-200a, NF-κB, estrogen receptor-positive breast cancer, endocrine therapy, positive feedback loop, biomarkers
MeSH terms
Enhancer of Zeste Homolog 2 Protein, Animals, Breast Neoplasms, Female, Humans, Tamoxifen, Signal Transduction, Gene Expression Regulation, Neoplastic, Hepatocyte Growth Factor, Antineoplastic Agents, Hormonal, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Feedback, Physiological, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice, RNA, Long Noncoding

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