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

biophysical properties breast cancer circulating tumor cells keratins metastasis truncated isoform

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
10 Nov 2023
Historique:
revised: 28 08 2023
received: 23 01 2023
medline: 11 11 2023
pubmed: 11 11 2023
entrez: 10 11 2023
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 37949677
doi: 10.1002/advs.202300509
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2300509

Subventions

Organisme : NIH HHS
ID : DP2 CA206653
Pays : United States

Informations de copyright

© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

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Auteurs

Diane S Kang (DS)

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.

Aidan Moriarty (A)

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.

Yiru Jess Wang (YJ)

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.

Amal Thomas (A)

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.

Jia Hao (J)

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

Bret A Unger (BA)

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

Remi Klotz (R)

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.

Shamim Ahmmed (S)

Department of Chemical Engineering, Texas Tech University, Lubbock, TX, 79409, USA.

Yonatan Amzaleg (Y)

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.

Stuart Martin (S)

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.

Siva Vanapalli (S)

Department of Chemical Engineering, Texas Tech University, Lubbock, TX, 79409, USA.

Ke Xu (K)

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

Andrew Smith (A)

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.

Keyue Shen (K)

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

Min Yu (M)

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.

Classifications MeSH