Cancers, Vol. 11, Pages 557: DIRAS3-Derived Peptide Inhibits Autophagy in Ovarian Cancer Cells by Binding to Beclin1

Cancers, Vol. 11, Pages 557: DIRAS3-Derived Peptide Inhibits Autophagy in Ovarian Cancer Cells by Binding to Beclin1 Cancers doi: 10.3390/cancers11040557 Authors: Margie N. Sutton Gilbert Y. Huang Xiaowen Liang Rajesh Sharma Albert S. Reger Weiqun Mao Lan Pang Philip J. Rask Kwangkook Lee Joshua P. Gray Amy M. Hurwitz Timothy Palzkill Steven W. Millward Choel Kim Zhen Lu Robert C. Bast Autophagy can protect cancer cells from acute starvation and enhance resistance to chemotherapy. Previously, we reported that autophagy plays a critical role in the survival of dormant, drug resistant ovarian cancer cells using human xenograft models and correlated the up-regulation of autophagy and DIRAS3 expression in clinical samples obtained during “second look” operations. DIRAS3 is an imprinted tumor suppressor gene that encodes a 26 kD GTPase with homology to RAS that inhibits cancer cell proliferation and motility. Re-expression of DIRAS3 in ovarian cancer xenografts also induces dormancy and autophagy. DIRAS3 can bind to Beclin1 forming the Autophagy Initiation Complex that triggers autophagosome formation. Both the N-terminus of DIRAS3 (residues 15–33) and the switch II region of DIRAS3 (residues 93–107) interact directly with BECN1. We have identified an autophagy-inhibiting peptide based on the switch II region of DIRAS3 linked to Tat peptide that is taken up by ovarian cancer cells, binds ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research