RRC ID |
18549
|
Author |
Sun PH, Zhu LM, Qiao MM, Zhang YP, Jiang SH, Wu YL, Tu SP.
|
Title |
The XAF1 tumor suppressor induces autophagic cell death via upregulation of Beclin-1 and inhibition of Akt pathway.
|
Journal |
Cancer Lett
|
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.
|
Volume |
310(2)
|
Pages |
170-80
|
Published |
2011-11-28
|
DOI |
10.1016/j.canlet.2011.06.037
|
PII |
S0304-3835(11)00394-6
|
PMID |
21788101
|
MeSH |
Adaptor Proteins, Signal Transducing
Adenoviridae / genetics
Animals
Apoptosis Regulatory Proteins / biosynthesis*
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Autophagy / genetics*
Beclin-1
Cell Line, Tumor
Female
Genes, Tumor Suppressor
Genetic Therapy / methods
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins / genetics
Membrane Proteins / biosynthesis*
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Proteins / biosynthesis*
Neoplasm Proteins / genetics
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Stomach Neoplasms / therapy*
Transfection
Up-Regulation
Xenograft Model Antitumor Assays
|
IF |
7.36
|
Times Cited |
24
|
WOS Category
|
ONCOLOGY
|
Resource |
Human and Animal Cells |
MKN45(RCB1001) |