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한양대학교

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Mol. Cancer, 16 October 2024 | https://doi.org/10.1186/s12943-024-02150-4 Tumor-intrinsic role of ICAM-1 in driving metastatic progression of triple-negative breast cancer through direct interaction with EGFR

Jae-Hyeok Kang ^1†, Nizam Uddin ^2†, Seungmo Kim ^1†, Yi Zhao ¹, Ki-Chun Yoo¹, Min-Jung Kim ³, Sung-Ah Hong ⁴, Sangsu Bae ⁵, Jeong-Yeon Lee ⁶, Incheol Shin ¹, Young Woo Jin ³, Heather M. O’Hagan ⁷, Joo Mi Yi^7,8* and Su-Jae Lee ^3*

¹Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, South Korea
²Center for Cell Analysis & Modeling, University of Connecticut Health Center, Farmington, CT 06030, USA
³Fibrosis and Cancer Targeting Biotechnology (FNCT BIOTECH), Toegye-Ro 36 Gil, Seoul 04626, South Korea
⁴Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, South Korea
⁵Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University, Seoul 03080, South Korea
⁶Department of Pathology, College of Medicine, Hanyang University, Seoul 04763, South Korea
⁷Department of Medical & Molecular Genetics, Indiana University School of Medicine, Bloomington, IN 47405, USA
⁸Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 47392, South Korea

^†These authors contributed equally
^*Corresponding authors: correspondence to Joo Mi Yi or Su-Jae Lee

Abstract

Triple-negative breast cancer (TNBC), the most aggressive subtype, presents a critical challenge due to the absence of approved targeted therapies. Hence, there is an urgent need to identify effective therapeutic targets for this condition. While epidermal growth factor receptor (EGFR) is prominently expressed in TNBC and recognized as a therapeutic target, anti-EGFR therapies have yet to gain approval for breast cancer treatment due to their associated side effects and limited efficacy. Here, we discovered that intercellular adhesion molecule-1 (ICAM-1) exhibits elevated expression levels in metastatic breast cancer and serves as a pivotal binding adaptor for EGFR activation, playing a crucial role in malignant progression. The activation of EGFR by tumor-expressed ICAM-1 initiates biased signaling within the JAK1/STAT3 pathway, consequently driving epithelial-to-mesenchymal transition and facilitating heightened metastasis without influencing tumor growth. Remarkably, ICAM-1-neutralizing antibody treatment significantly suppressed cancer metastasis in a breast cancer orthotopic xenograft mouse model. In conclusion, our identification of ICAM-1 as a novel tumor intrinsic regulator of EGFR activation offers valuable insights for the development of TNBC-specific anti-EGFR therapies.

논문정보

형식Research article
게재일2024년 10월 (BRIC 등록일 2024-10-17)
연구진국내(교신)+국외 연구진
분야 생명과학 > 분자생물학

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