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HIF-2α regulates non-canonical glutamine metabolism via activation of PI3K/ mTORC2 pathway in human pancreatic ductal adenocarcinoma.
- Source :
- Journal of Cellular & Molecular Medicine; Nov2017, Vol. 21 Issue 11, p2896-2908, 13p
- Publication Year :
- 2017
-
Abstract
- Hypoxia-inducible factor-2α ( HIF-2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma ( PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat-sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF-2α expression was significantly up-regulated in PDAC, positively associated with disease stage, lymph-node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients. We demonstrated that HIF-2α silencing could reduce proliferation, migration and invasion of PDAC cells in vitro. The similar effect on growth was demonstrated in vivo. Furthermore, we noted that knock-down of HIF-2α significantly decreased the expression of glutamate oxaloacetate transaminase 1 ( GOT1). Importantly, we confirmed that the PI3K/ mTORC2 pathway promoted GOT1 expression by targeting HIF-2α. Our study validated HIF-2α was an important factor in PDAC progression and poor prognosis and may promote non-canonical glutamine metabolism via activation of PI3K/ mTORC2 pathway. Targeting HIF-2α represents a novel prognostic biomarker and therapeutic target for patients with PDAC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15821838
- Volume :
- 21
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Journal of Cellular & Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 125996123
- Full Text :
- https://doi.org/10.1111/jcmm.13202