PTP1B regulates non-mitochondrial oxygen consumption via RNF213 to promote tumour survival during hypoxia

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PTP1B regulates non-mitochondrial oxygen consumption via RNF213 to promote tumour survival during hypoxia

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Title: PTP1B regulates non-mitochondrial oxygen consumption via RNF213 to promote tumour survival during hypoxia
Author: Banh, Robert S.; Iorio, Caterina; Marcotte, Richard; Xu, Yang; Cojocari, Dan; Rahman, Anas Abdel; Pawling, Judy; Zhang, Wei; Sinha, Ankit; Rose, Christopher M.; Isasa, Marta; Zhang, Shuang; Wu, Ronald; Virtanen, Carl; Hitomi, Toshiaki; Habu, Toshiyuki; Sidhu, Sachdev S.; Koizumi, Akio; Wilkins, Sarah E.; Kislinger, Thomas; Gygi, Steven P.; Schofield, Christopher J.; Dennis, James W.; Wouters, Bradly G.; Neel, Benjamin G.

Note: Order does not necessarily reflect citation order of authors.

Citation: Banh, R. S., C. Iorio, R. Marcotte, Y. Xu, D. Cojocari, A. A. Rahman, J. Pawling, et al. 2016. “PTP1B regulates non-mitochondrial oxygen consumption via RNF213 to promote tumour survival during hypoxia.” Nature cell biology 18 (7): 803-813. doi:10.1038/ncb3376. http://dx.doi.org/10.1038/ncb3376.
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Abstract: Tumours exist in a hypoxic microenvironment and must limit excessive oxygen consumption. Hypoxia-inducible factor controls mitochondrial oxygen consumption, but how/if tumours regulate non-mitochondrial oxygen consumption (NMOC) is unknown. Protein-Tyrosine Phosphatase-1B (PTP1B) is required for Her2/Neu-driven breast cancer (BC) in mice, though the underlying mechanism and human relevance remain unclear. We found that PTP1B-deficient HER2+ xenografts have increased hypoxia, necrosis and impaired growth. In vitro, PTP1B deficiency sensitizes HER2+ BC lines to hypoxia by increasing NMOC by α-KG-dependent dioxygenases (α-KGDDs). The Moyamoya disease gene product RNF213 , an E3 ligase, is negatively regulated by PTP1B in HER2+ BC cells. RNF213 knockdown reverses the effects of PTP1B-deficiency on α-KGDDs, NMOC and hypoxia-induced death of HER2+ BC cells, and partially restores tumourigenicity. We conclude that PTP1B acts via RNF213 to suppress α-KGDD activity and NMOC. This PTP1B/RNF213/α-KGDD pathway is critical for survival of HER2+ BC, and possibly other malignancies, in the hypoxic tumour microenvironment.
Published Version: doi:10.1038/ncb3376
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936519/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29739007
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