4.8 Article

Beclin 1 Promotes Endosome Recruitment of Hepatocyte Growth Factor Tyrosine Kinase Substrate to Suppress Tumor Proliferation

Journal

CANCER RESEARCH
Volume 80, Issue 2, Pages 249-262

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-19-1555

Keywords

-

Categories

Funding

  1. NIH [CA177167, CA206378, CA16672]

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available