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Contributions of the distinct biophysical phenotype of polyploidal giant cancer cells to cancer progression.
Xuan, Botai; Ghosh, Deepraj; Dawson, Michelle R.
Afiliação
  • Xuan B; Brown University, Department of Molecular Pharmacology, Physiology, & Biotechnology, Providence, 02912, USA.
  • Ghosh D; Brown University, Department of Molecular Pharmacology, Physiology, & Biotechnology, Providence, 02912, USA.
  • Dawson MR; Brown University, Department of Molecular Pharmacology, Physiology, & Biotechnology, Providence, 02912, USA; Brown University, Center for Biomedical Engineering, Providence, 02912, USA; Brown University, School of Engineering, Providence, 02912, USA. Electronic address: Michelle_Dawson@Brown.edu.
Semin Cancer Biol ; 81: 64-72, 2022 06.
Article em En | MEDLINE | ID: mdl-33992783
Polyploid giant cancer cells (PGCCs) are a commonly observed histological feature of human tumors and are particularly prominent in late stage and drug resistant cancers. The chromosomal duplication conferred by their aneuploidy gives rise to DNA damage resistance and complex tumor cell karyotypes, a driving factor in chemotherapy resistance and disease relapse. Furthermore, PGCCs also exhibit key cytoskeletal features that give rise to a distinct biophysical phenotype, including increased density of polymerized actin and vimentin intermediate filaments, nuclear and cytoskeletal stiffening, increased traction force, and migratory persistence. Despite recent research highlighting the role PGCCs play in cancer progression, this population of tumor cells remains poorly characterized in terms of their biophysical properties. In this review, we will discuss the various aspects of their biomolecular phenotype, such as increased stemness as well as a mixed EMT signature. These features have been extensively associated with tumorigenesis and recurrence, and aggressive cancers. Additionally, we will also examine the distinct PGCC cytoskeletal features of actin and filamentous vimentin. Specifically, how the differential organization of these networks serve to support their increased size and drive migratory persistence. These findings could shed light on potential therapeutic strategies that allow for specific elimination or mitigation of the invasive potential of these polyploid cancer cells. Lastly, we will examine how the biophysical and molecular phenotype of PGCCs combine to tip the scale in favor of promoting cancer progression, presenting an important target in the clinical treatment of cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Actinas / Neoplasias Limite: Humans Idioma: En Revista: Semin Cancer Biol Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Actinas / Neoplasias Limite: Humans Idioma: En Revista: Semin Cancer Biol Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos