Journal
CANCER LETTERS
Volume 420, Issue -, Pages 38-48Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.01.067
Keywords
LZT52; p85; PI3K; Radioresistance; Nasopharyngeal carcinoma
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Funding
- National Natural Science Foundation of China [81672289, 81672978]
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Phosphoinositide 3-kinase (PI3K) activity is aberrantly activated in nasopharyngeal carcinoma. However, the underlying mechanisms remain unclear. Here, we found that Leucine zipper tumor suppressor 2 (LZTS2) was downregulated and predicted poor prognosis in nasopharyngeal carcinoma patients. Furthermore, we identified the PI3K subunit p85 as a novel LZTS2-interacting protein using an unbiased proteomics approach. Moreover, we demonstrated that LZTS2 competes with p110 for p85 binding and inhibits activation of the PI3K/AKT signaling pathway. Functionally, we showed that LZTS2 suppresses tumorigenesis and radioresistance in nasopharyngeal carcinoma in a p85-dependent manner. Taken together, our results not only provide understanding of the molecular mechanisms by which PI3K/AKT signaling is activated but also suggest that targeting the LZTS2/PI3K/AKT signaling axis is a promising therapeutic strategy for radiosensitization of nasopharyngeal carcinoma. (C) 2018 Elsevier B.V. All rights reserved.
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