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journal article·2024-02Open access

Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity

Diane S. Kang, Aidan Moriarty, Yiru Jess Wang, Amal Thomas, Jia Hao, Bret A. Unger, Remi Klotz, Shamim Ahmmed, Yonatan Amzaleg, Stuart Martin, Siva Vanapalli, Ke Xu, Andrew Smith, Keyue Shen, Min Yu

Advanced Science· Volume 11· Issue 5
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Source abstract

Abstract

Abstract Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient‐derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.
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Research context

OpenAlex topics: Skin and Cellular Biology Research · Cellular Mechanics and Interactions · Microtubule and mitosis dynamics

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

Affiliations

Department of Stem Cell Biology and Regenerative Medicine Keck School of Medicine of the University of Southern California Los Angeles CA 90033 USA

USC Norris Comprehensive Cancer Center Keck School of Medicine of the University of Southern California Los Angeles CA 90033 USA

Department of Pharmacology University of Maryland School of Medicine Baltimore MD 21201 USA

Marlene and Stewart Greenebaum Comprehensive Cancer Center University of Maryland School of Medicine Baltimore MD 21201 USA

Department of Molecular and Computational Biology USC David and Dana Dornsife College of Letters Arts and Sciences University of Southern California Los Angeles CA 90089 USA

Department of Biomedical Engineering Viterbi School of Engineering University of Southern California Los Angeles CA 90089 USA

Department of Chemistry University of California at Berkeley Berkeley CA 94720 USA

Department of Chemical Engineering Texas Tech University Lubbock TX 79409 USA

Funding

National Institutes of Health · Alexander and Margaret Stewart Trust · Pew Charitable Trusts

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