The Solute Carrier MFSD1 Decreases the Activation Status of β1 Integrin and Thus Tumor Metastasis

Marko Roblek, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, Daria E Siekhaus

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

Abstract

Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier Major Facilitator Superfamily Domain-containing protein 1 (MFSD1) in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in experimental and spontaneous metastasis mouse models. We identified an increased migratory potential in MFSD1 -/- tumor cells which was mediated by increased focal adhesion turnover, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, downregulation of MFSD1 expression was observed during the early steps of tumorigenesis, and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor cell dissemination.

OriginalspracheEnglisch
Aufsatznummer777634
Seiten (von - bis)777634
FachzeitschriftFrontiers in Oncology
Jahrgang12
DOIs
PublikationsstatusVeröffentlicht - 8 Feb. 2022
Extern publiziertJa

IMC Forschungsschwerpunkte

  • Medical biotechnology

ÖFOS 2012 - Österreichischen Systematik der Wissenschaftszweige

  • 304005 Medizinische Biotechnologie

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