PIWIL2 interacting with IKK to regulate autophagy and apoptosis in esophageal squamous cell carcinoma
| Autor: | Wenhao Jiang, Lian Huang, Yunqiang Liu, Yilu Lu, Dachang Tao, Yue Song, Xu Zhao, Bojun Qiu, Yongxin Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Mice Nude Apoptosis mTORC1 IκB kinase Biology medicine.disease_cause Transfection Article Prognostic markers Mice Cell Line Tumor Macroautophagy medicine Autophagy Biomarkers Tumor Animals Humans Molecular Biology Cancer genetics Cell Proliferation Cancer Cell Biology ULK1 Middle Aged medicine.disease digestive system diseases Argonaute Proteins Cancer research Phosphorylation Esophageal Squamous Cell Carcinoma Carcinogenesis |
| Zdroj: | Cell Death and Differentiation |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and cause of death from cancer in China. Previous studies showed that autophagy and apoptosis inhibition are critical for the survival of ESCC cells. However, the underlying mechanisms remain to be clarified. Recently, we found that PIWIL2, a novel cancer testis protein, is highly expressed in ESCC and associated with high T-stage and poor 5-year survival rate in patients. Our further study showed that PIWIL2 can directly bind to IKK and promote its phosphorylation, leading to phosphorylation of IκB and subsequently nuclear translocation of NF-κB for apoptosis inhibition. Meanwhile, PIWIL2 competitively inhibits binding of IKK to TSC1, and thus deactivate mTORC1 pathway which suppresses ULK1 phosphorylation and initiation of autophagy. The mouse xenograft model suggested that PIWIL2 can promote ESCC growth in an IKK-dependent manner. This present work firstly revealed that PIWIL2 can play a role in regulating autophagy and apoptosis, and is associated with poor prognosis in ESCC patients, providing novel insights into the roles of PIWIL2 in tumorigenesis. |
| Databáze: | OpenAIRE |
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