LC3C-Mediated Autophagy Selectively Regulates the Met RTK and HGF-Stimulated Migration and Invasion

Emily S. Bell, Paula Pinto Coelho, Colin D.H. Ratcliffe, Charles V. Rajadurai, Pascal Peschard, Richard Vaillancourt, Dongmei Zuo, Morag Park

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The Met/hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) is deregulated in many cancers and is a recognized target for cancer therapies. Following HGF stimulation, the signaling output of Met is tightly controlled by receptor internalization and sorting for degradation or recycling. Here, we uncover a role for autophagy in selective degradation of Met and regulation of Met-dependent cell migration and invasion. Met engagement with the autophagic pathway is dependent on complex formation with the mammalian ATG8 family member MAP1LC3C. LC3C deletion abrogates Met entry into the autophagy-dependent degradative pathway, allowing identification of LC3C domains required for rescue. Cancer cells with low LC3C levels show enhanced Met stability, signaling, and cell invasion. These findings provide mechanistic insight into RTK recruitment to autophagosomes and establish distinct roles for ATG8 proteins in this process, supporting that differential expression of ATG8 proteins can shape the functional consequences of autophagy in cancer development and progression.

Original languageEnglish (US)
Pages (from-to)4053-4068.e6
JournalCell Reports
Volume29
Issue number12
DOIs
StatePublished - Dec 17 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Bell, E. S., Coelho, P. P., Ratcliffe, C. D. H., Rajadurai, C. V., Peschard, P., Vaillancourt, R., Zuo, D., & Park, M. (2019). LC3C-Mediated Autophagy Selectively Regulates the Met RTK and HGF-Stimulated Migration and Invasion. Cell Reports, 29(12), 4053-4068.e6. https://doi.org/10.1016/j.celrep.2019.11.063