Beclin 1 Promotes Endosome Recruitment of Hepatocyte Growth Factor Tyrosine Kinase Substrate to Suppress Tumor Proliferation
Authors
Matthew-Onabanjo, Asia NJanusis, Jenny
Mercado-Matos, Jose
Carlisle, Anne E.
Kim, Dohoon
Levine, Fayola
Cruz-Gordillo, Peter
Richards, Ryan
Lee, Michael J
Shaw, Leslie M.
UMass Chan Affiliations
Program in Molecular MedicineGraduate School of Biomedical Sciences, MD/PhD Program
Program in Systems Biology
Medical Scientist Training Program
Department of Molecular, Cell and Cancer Biology
Document Type
Journal ArticlePublication Date
2020-01-15
Metadata
Show full item recordAbstract
Beclin 1 has nonautophagic functions that include its ability to regulate endocytic receptor trafficking. However, the contribution of this function to tumor suppression is poorly understood. Here, we provide in vivo evidence that Beclin 1 suppresses tumor proliferation by regulating the endocytic trafficking and degradation of the EGFR and transferrin (TFR1) receptors. Beclin 1 promoted endosomal recruitment of hepatocyte growth factor tyrosine kinase substrate (HRS), which was necessary for sorting surface receptors to intraluminal vesicles for signal silencing and lysosomal degradation. In tumors with low Beclin 1 expression, endosomal HRS recruitment was diminished and receptor function was sustained. Collectively, our results demonstrate a novel role for Beclin 1 in impeding tumor growth by coordinating the regulation of key growth factor and nutrient receptors. These data provide an explanation for how low levels of Beclin 1 facilitate tumor proliferation and contribute to poor cancer outcomes. SIGNIFICANCE: Beclin 1 controls the trafficking fate of growth regulatory receptors to suppress tumor proliferation.Source
Cancer Res. 2020 Jan 15;80(2):249-262. doi: 10.1158/0008-5472.CAN-19-1555. Epub 2019 Nov 19. Link to article on publisher's site
DOI
10.1158/0008-5472.CAN-19-1555Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49891PubMed ID
31744816Related Resources
ae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-19-1555