Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5589240 | Gene | 2017 | 6 Pages |
Abstract
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 4β (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.
Keywords
Bcl-2LAPTM4BUVRAGTKIIFN-γEGFRMCsPBSPI3KBSAB-cell CLL/lymphoma 2CRISPR-Casbovine serum albuminHERTandem affinity purificationTAPPhosphate buffered salinephosphoinositide 3-kinaseTyrosine kinase inhibitorwild typemultiple cloning site(s)Interferon gammahuman epidermal growth factor receptorEpidermal growth factor receptor
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Authors
Miao Tian, Yu Chen, Dan Tian, Xiaofang Qiao, Zhiming Ma, Jinlong Li,