論文 - 詳細
| RRC ID | 18549 |
|---|---|
| 著者 | Sun PH, Zhu LM, Qiao MM, Zhang YP, Jiang SH, Wu YL, Tu SP. |
| タイトル | The XAF1 tumor suppressor induces autophagic cell death via upregulation of Beclin-1 and inhibition of Akt pathway. |
| ジャーナル | 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. |
| 巻・号 | 310(2) |
| ページ | 170-80 |
| 公開日 | 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 |
| 引用数 | 24 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |