期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 44, 页码 18892-18897出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1004952107
关键词
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资金
- National Basic Research Program of China [2010CB912102, 2010CB529703]
- National Natural Science Foundation of China [30740084, 30871284, 30971495]
- Chinese Academy of Sciences [2008KIP101, 2008KIP102]
- Science and Technology Commission of Shanghai Municipality [08PJ14105]
LKB1 loss-of-function mutations, observed in similar to 30% of human lung adenocarcinomas, contribute significantly to lung cancer malignancy progression. We show that lysyl oxidase ( LOX), negatively regulated by LKB1 through mTOR-HIF-1 alpha signaling axis, mediates lung cancer progression. Inhibition of LOX activity dramatically alleviates lung cancer malignancy progression. Up-regulated LOX expression triggers excess collagen deposition in Lkb1-deficient lung tumors, and thereafter results in enhanced cancer cell proliferation and invasiveness through activation of beta 1 integrin signaling. High LOX level and activity correlate with poor prognosis and metastasis. Our findings provide evidence of how LKB1 loss of function promotes lung cancer malignancy through remodeling of extracellular matrix microenvironment, and identify LOX as a potential target for disease treatment in lung cancer patients.
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