Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Lett. 2011 Nov 28;310(2):170-80. doi: 10.1016/j.canlet.2011.06.037. Epub 2011 Jul 5.

The XAF1 tumor suppressor induces autophagic cell death via upregulation of Beclin-1 and inhibition of Akt pathway.

Author information

  • 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, People's Republic of China.

Abstract

Autophagy is designated as type II programmed cell death and may confer a tumor-suppressive function. Our previous studies have shown that XIAP-associated factor 1 (XAF1) induced apoptosis and inhibited tumor growth in gastric cancer cells. In this study, we investigated the effect of XAF1 on the induction of autophagy in gastric cancer cells. We found that adenovirus vector-mediated XAF1 (adeno-XAF1) expression markedly induced autophagy, upregulated the level of Beclin-1 and inhibited phospho-Akt and phospho-p70S6K in gastric cancer cells. The downregulation of Beclin 1 or 3-methyladenine treatment suppressed adeno-XAF1-induced autophagy, but significantly enhanced adeno-XAF1-induced apoptosis. A pan-caspase inhibitor prevented adeno-XAF1-induced apoptosis, but significantly increased adeno-XAF1-induced autophagy. Furthermore, adeno-XAF1 induced autophagy in xenograft tumor and inhibited tumor growth. Our results document that adeno-XAF1 induces autophagy through upregulation of Beclin 1 expression and inhibition of Akt/p70S6K pathway, and reveal a new mechanism of XAF1 tumor suppression.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID:
21788101
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk