In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3303-3303
Kurzfassung:
Survivin, a member of the inhibitors-of-apoptosis proteins family, is highly expressed in different cancers and its expression is correlated with tumorigenesis and tumor metastasis. At the cellular and molecular levels, Survivin is a dual functions protein that promotes mitosis and also inhibits apoptosis. In this study, we found that Survivin is a novel negative-regulator of autophagy. Molecular analysis and computational modeling revealed that Survivin negatively regulates the formation of Atg5-Atg12 conjugates, which plays important roles in the process of autophagosome elongation, in breast cancer cells. It also negatively regulates the expression and activity of cathepsin L in cells. Interestingly, we found that Survivin binds to p62/SQSTM1 and LC3B and is also an autophagic substrate protein, in which its expression is in part directly regulated by autophagy at the protein level. Finally, mechanistic study revealed YM155, a Survivin inhibitor that was originally developed to inhibit Survivin gene transcription, downregulates Survivin expression in part through autophagic protein degradation. Taken together, findings of this study provide new mechanistic insights into both molecular functions and regulations of Survivin and the molecular mechanism of actions of YM155, a drug currently undergoing clinical trials for cancer treatment. Citation Format: Hsiu-Han Chan, Mohane Selvaraj Coumar, Siao-Muk Cheng, Shing-Ling Tsai, Chun-Hui Lin, Shang-Hung Chen, Euphemia Leung, Chun Hei Antonio Cheung. Survivin negatively-regulates autophagy through interference with the formation of Atg5-Atg12-Atg16L complex in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3303. doi:10.1158/1538-7445.AM2017-3303
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-3303
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2017
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
