The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers

Q: What is the study’s central focus regarding EP300, F11R, and EMT in triple-negative breast cancer?

The work evaluates how activation of EP300 by F11R relates to EMT and whether this pathway can serve as a prognostic indicator in triple-negative breast cancers.

Q: How was F11R linked to prognosis in breast cancer?

mRNA analyses using TCGA and protein assessment in patient tissue array cohorts showed that higher F11R levels correspond to poorer overall survival and/or disease-free survival.

Q: Which subtype patterns were reported for F11R expression and associated poor prognosis?

F11R mRNA and protein levels were reported to increase in HER2-enriched and basal-like tumors, and high F11R was associated with poor prognosis across luminal, HER2-positive, and triple-negative breast cancer subtypes.

Sep 24, 2026

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Cancer progression is shaped by junctional adhesion molecule (JAM) family members. Using The Cancer Genome Atlas, JAM expression was analyzed across cancer types, linking F11R (F11 receptor) mRNA in tumors with inverse JAM-2 and JAM-3 expression specifically in breast cancer, associated with poor prognosis. A 50-gene molecular signature subtyped breast cancer, showing increased F11R in HER2-enriched and basal-like tumors. Tissue array and immunohistochemistry demonstrated high F11R protein correlates with worse survival in multiple cohorts, and pathway analysis implicated EP300 and suggested drug repurposing candidates for F11R-positive disease.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Abstract

Introduction

Breast cancer subtypes and clinical significance

The Journal of Pathology: Clinical Research J Pathol Clin Res May 2023; 9: 165–181 Published online 13 February 2023 in Wiley Online Library (wi[leyonlinelibrary.com](leyonlinelibrary.com). DOI: 10.1002/cjp2.313)[).](leyonlinelibrary.com). DOI: 10.1002/cjp2.313)[ DOI: 10.1002/cjp2.313](leyonlinelibrary.com). DOI: 10.1002/cjp2.313) ORIGINAL ARTICLE The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers Chien-Hsiu Li 1† , Chih-Yeu Fang2† , Ming-Hsien Chan 1 , Pei-Jung Lu3,4 , Luo-Ping Ger5,6, Jan-Show Chu7,8 , Yu-Chan Chang9* , Chi-Long Chen7,8* and Michael Hsiao 1,10* 1 Genomics Research Center, Academia Sinica, Taipei, Taiwan 2National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan 4Clinical Medicine Research Center, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan 5Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 6Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 7Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 8Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan 9Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan 10Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan *Correspondence to: Michael Hsiao, Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, [Taiwan. E-mail:](Taiwan. E-mail: mhsiao@gate.sincia.edu.tw)[ mhsiao@gate.sincia.edu.tw](Taiwan. E-mail: mhsiao@gate.sincia.edu.tw); Chi-Long Chen, Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. E-mail: [chencl@tmu.edu.tw](chencl@tmu.edu.tw); and Yu-Chan Chang, Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, [Taiwan. E-mail:](Taiwan. E-mail: jameskobe0@gmail.com)[ jameskobe0@gmail.com](Taiwan. E-mail: jameskobe0@gmail.com) †These authors contributed equally to this work. Abstract Cancer progression is inﬂuenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with poor prognosis (p = 0.024, hazard ratio = 1.44 [1.05–1.99]). A 50-gene molecular signature (prediction analysis of microarray 50) was used to subtype BCa. F11R mRNA expression signiﬁcantly increased in human epidermal growth factor receptor 2 (HER2)-enriched (p = 0.0035) and basal-like BCa tumours(p = 0.0005). We evaluated F11R protein levels in two different compositions of BCa subtype patient tissue array cohorts to determine the relationship between BCa subtype and prognosis. Immunohistochemistry staining revealed that a high F11R protein level was associated with poor overall survival (p < 0.001; Taipei Medical University [TMU] cohort, p < 0.001; Kaohsiung Veterans General Hospital [KVGH] cohort) or disease-free survival (p < 0.001 [TMU cohort], p = 0.034 [KVGH cohort]) in patients with BCa. Comparison of F11R levels in different subtypes revealed the association of poor prognosis with high levels of F11R among luminal (p < 0.001 [TMU cohort], p = 0.027 [KVGH cohort]), HER2 positive (p = 0.018 [TMU cohort], p = 0.037 [KVGH cohort]), and triple-negative (p = 0.013 [TMU cohort], p = 0.037 [

FAQs

What is the study’s central focus regarding EP300, F11R, and EMT in triple-negative breast cancer?

The work evaluates how activation of EP300 by F11R relates to EMT and whether this pathway can serve as a prognostic indicator in triple-negative breast cancers.

How was F11R linked to prognosis in breast cancer?

mRNA analyses using TCGA and protein assessment in patient tissue array cohorts showed that higher F11R levels correspond to poorer overall survival and/or disease-free survival.

Which subtype patterns were reported for F11R expression and associated poor prognosis?

F11R mRNA and protein levels were reported to increase in HER2-enriched and basal-like tumors, and high F11R was associated with poor prognosis across luminal, HER2-positive, and triple-negative breast cancer subtypes.

Sep 24, 2026

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