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A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression.
Ghannoum, Salim; Fantini, Damiano; Zahoor, Muhammad; Reiterer, Veronika; Phuyal, Santosh; Leoncio Netto, Waldir; Sørensen, Øystein; Iyer, Arvind; Sengupta, Debarka; Prasmickaite, Lina; Mælandsmo, Gunhild Mari; Köhn-Luque, Alvaro; Farhan, Hesso.
Afiliação
  • Ghannoum S; Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Oslo, Norway.
  • Fantini D; Department of Urology, Northwestern University, Chicago, Illinois, United States of America.
  • Zahoor M; Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Oslo, Norway.
  • Reiterer V; Institute of Pathophysiology, Medical University of Innsbruck, Innsbruck, Austria.
  • Phuyal S; Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, Oslo, Norway.
  • Leoncio Netto W; Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Sørensen Ø; Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
  • Iyer A; Department of Computational Biology, University of Lausanne (UNIL), Lausanne, Switzerland.
  • Sengupta D; Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
  • Prasmickaite L; Centre for Artificial Intelligence, Indraprastha Institute of Information Technology, Delhi, India.
  • Mælandsmo GM; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
  • Köhn-Luque A; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
  • Farhan H; Department of Medical Biology, UiT-The Arctic University of Norway, Tromsø, Norway.
PLoS Comput Biol ; 19(4): e1010995, 2023 04.
Article em En | MEDLINE | ID: mdl-37068117
Our understanding of how speed and persistence of cell migration affects the growth rate and size of tumors remains incomplete. To address this, we developed a mathematical model wherein cells migrate in two-dimensional space, divide, die or intravasate into the vasculature. Exploring a wide range of speed and persistence combinations, we find that tumor growth positively correlates with increasing speed and higher persistence. As a biologically relevant example, we focused on Golgi fragmentation, a phenomenon often linked to alterations of cell migration. Golgi fragmentation was induced by depletion of Giantin, a Golgi matrix protein, the downregulation of which correlates with poor patient survival. Applying the experimentally obtained migration and invasion traits of Giantin depleted breast cancer cells to our mathematical model, we predict that loss of Giantin increases the number of intravasating cells. This prediction was validated, by showing that circulating tumor cells express significantly less Giantin than primary tumor cells. Altogether, our computational model identifies cell migration traits that regulate tumor progression and uncovers a role of Giantin in breast cancer progression.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Proteínas de Membrana Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Proteínas de Membrana Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article