A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_3C3B7E71A649
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression.
Journal
PLoS computational biology
Author(s)
Ghannoum S., Fantini D., Zahoor M., Reiterer V., Phuyal S., Leoncio Netto W., Sørensen Ø., Iyer A., Sengupta D., Prasmickaite L., Mælandsmo G.M., Köhn-Luque A., Farhan H.
ISSN
1553-7358 (Electronic)
ISSN-L
1553-734X
Publication state
Published
Issued date
04/2023
Peer-reviewed
Oui
Volume
19
Number
4
Pages
e1010995
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Pubmed
Open Access
Yes
Create date
25/04/2023 14:18
Last modification date
19/07/2023 7:09
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