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

doi:10.1002/advs.202300509

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

Adv Sci (Weinh). 2024 Feb;11(5):e2300509. doi: 10.1002/advs.202300509. Epub 2023 Nov 10.

Authors

Diane S Kang^{1

2}, Aidan Moriarty^{1

2

3

4}, Yiru Jess Wang^{1

2

3

4}, Amal Thomas⁵, Jia Hao⁶, Bret A Unger⁷, Remi Klotz^{1

2

3

4}, Shamim Ahmmed⁸, Yonatan Amzaleg^{1

2}, Stuart Martin^{3

4}, Siva Vanapalli⁸, Ke Xu⁷, Andrew Smith⁵, Keyue Shen⁶, Min Yu^{1

2

3

4}

Affiliations

¹ Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, 90033, USA.
² USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA, 90033, USA.
³ Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
⁴ Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
⁵ 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.
⁶ Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
⁷ Department of Chemistry, University of California at Berkeley, Berkeley, CA, 94720, USA.
⁸ Department of Chemical Engineering, Texas Tech University, Lubbock, TX, 79409, USA.

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.

Keywords: biophysical properties; breast cancer; circulating tumor cells; keratins; metastasis; truncated isoform.

MeSH terms

Breast Neoplasms* / metabolism
Breast Neoplasms* / pathology
Ectopic Gene Expression
Female
Humans
Keratins, Hair-Specific* / genetics
Keratins, Hair-Specific* / metabolism
Protein Isoforms / genetics

Substances

Keratins, Hair-Specific
Protein Isoforms
KRT81 protein, human

Abstract

MeSH terms

Substances

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