Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells

Beclin1 is an essential autophagy regulator and a haploinsufficient tumor-suppressor. Reduced Berclin1 expression has been associated with many types of human malignancies including gastric cancer. However, the mechanism of how Beclin1 represses tumorigenesis of gastric cancer remains elusive. In recent proteomics study, we found that Beclin1 is associated with Lysosome-associated transmembrane protein 40 (LAPTM4B). LAPTM4B plays an important role in promoting the growth and proliferation of tumor cells, it is overexpressed in a variety of solid tumors and serves as a biomarker for tumor therapy. Further analysis showed that Beclin1 interacts with both the N- and C-termini of LAPTM4B and this interaction is independent of Vps34 complex. We demonstrated that Beclin1 competes with Epidermal growth factor receptor (EGFR) for LAPTM4B binding and Beclin1 can repress the LAPTM4B mediated EGFR activation and gastric cancer cell growth. Taken together, our study proposes a role of Beclin1 in repressing gastric cancer through disrupting the oncogenic promoting function of LAPTM4B.