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KIF16B drives MT1-MMP recycling in macrophages and promotes co-invasion of cancer cells.
Hey, Sven; Wiesner, Christiane; Barcelona, Bryan; Linder, Stefan.
Afiliação
  • Hey S; Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, Hamburg, Germany.
  • Wiesner C; Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, Hamburg, Germany.
  • Barcelona B; Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, Hamburg, Germany.
  • Linder S; Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, Hamburg, Germany s.linder@uke.de.
Life Sci Alliance ; 6(11)2023 11.
Article em En | MEDLINE | ID: mdl-37696580
The matrix metalloproteinase MT1-MMP is a central effector of cellular proteolysis. Accordingly, regulation of the surface-localized pool of MT1-MMP is crucial for cell migration and invasion. Here, we identify the superprocessive kinesin KIF16B as a major driver of fast recycling of MT1-MMP to the surface of primary human macrophages. KIF16B associates with MT1-MMP on Rab14-positive vesicles, and its depletion results in strongly reduced MT1-MMP surface levels, as shown by microscopical, biochemical, and cell-sorting approaches. As a consequence, KIF16B-depleted macrophages exhibit strongly reduced matrix degradation and invasion. We further identify the cargo-binding C-terminus of KIF16B as a critical element of MT1-MMP transport, as its overexpression uncouples MT1-MMP vesicles from the endogenous motor, thus leading to a reduction of surface-associated MT1-MMP and to reduced matrix degradation and invasion. Importantly, depletion of KIF16B in primary macrophages also reduces the co-invasion of cancer cells from tumor spheroids, pointing to the KIF16B-driven recycling pathway in macrophages as an important regulatory element of the tumor microenvironment.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cinesinas / Metaloproteinase 14 da Matriz / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cinesinas / Metaloproteinase 14 da Matriz / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article