Surface Keratin 1, A Tumor-Selective Peptide Target in Human Triple-Negative Breast Cancer

Authors

Shih-Jing Yao, Chapman University
Farideh Amirrad, Chapman UniversityFollow
Elmira Ziaei, Chapman UniversityFollow
Azam Saghaeidehkordi, Chapman UniversityFollow
Moom R. Roosan, Chapman UniversityFollow
Kiumars Shamloo, Chapman UniversityFollow
Ajay Sharma, Chapman UniversityFollow
Rachita K. Sumbria, Chapman UniversityFollow
Surya M. Nauli, Chapman UniversityFollow
Christopher G. Bunick, Yale University
Kamaljit Kaur, Chapman UniversityFollow

Document Type

Article

Publication Date

7-1-2025

Abstract

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal mammary epithelial cells to detect K1 from cell lysates using three methods: mass spectrometry, peptide mass fingerprinting, and Western blot. TNBC cell lysates confirmed the presence and high expression levels of 67 kDa K1. Importantly, intact cells showed that K1 is uniformly present on the surface of TNBC cells, while no or minimal cell-surface K1 was found in normal mammary epithelial cells using immunofluorescence confocal microscopy. Further, we show that cell-surface K1 was utilized by TNBC-selective peptide 18–4 for its uptake via cell-surface receptor (K1)-mediated endocytosis in TNBC cells, and the presence of peptide 18–4 did not affect the assembly of endogenous cytoplasmic K1. Taken together, our results demonstrate that K1 is overexpressed in human TNBC, and cell-surface K1 represents a promising new target for directed delivery in TNBC using targeting ligands such as peptide 18–4.

Comments

This article was originally published in Scientific Reports, volume 15, in 2025. https://doi.org/10.1038/s41598-025-05351-z

This article was the recipient of a Chapman University Supporting Open Access Research and Scholarship (SOARS) award.

Recommended Citation

Yao, SJ., Amirrad, F., Ziaei, E. et al. Surface keratin 1, a tumor-selective peptide target in human triple-negative breast cancer. Sci Rep 15, 21644 (2025). https://doi.org/10.1038/s41598-025-05351-z

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The authors

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.