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The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer.

Author(s): Jin, Lingtao; Chun, Jaemoo; Pan, Chaoyun; Kumar, Avi; Zhang, Guojing; et al

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dc.contributor.authorJin, Lingtao-
dc.contributor.authorChun, Jaemoo-
dc.contributor.authorPan, Chaoyun-
dc.contributor.authorKumar, Avi-
dc.contributor.authorZhang, Guojing-
dc.contributor.authorHa, Youna-
dc.contributor.authorLi, Dan-
dc.contributor.authorAlesi, Gina N.-
dc.contributor.authorKang, Yibin-
dc.contributor.authorZhou, Lu-
dc.contributor.authorYu, Wen-Mei-
dc.contributor.authorMagliocca, Kelly R.-
dc.contributor.authorKhuri, Fadlo R.-
dc.contributor.authorQu, Cheng-Kui-
dc.contributor.authorMetallo, Christian-
dc.contributor.authorOwonikoko, Taofeek K.-
dc.contributor.authorKang, Sumin-
dc.date.accessioned2020-02-26T18:27:51Z-
dc.date.available2020-02-26T18:27:51Z-
dc.date.issued2018-01-04en_US
dc.identifier.citationJin, Lingtao, Chun, Jaemoo, Pan, Chaoyun, Kumar, Avi, Zhang, Guojing, Ha, Youna, Li, Dan, Alesi, Gina N, Kang, Yibin, Zhou, Lu, Yu, Wen-Mei, Magliocca, Kelly R, Khuri, Fadlo R, Qu, Cheng-Kui, Metallo, Christian, Owonikoko, Taofeek K, Kang, Sumin. (2018). The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer.. Molecular cell, 69 (1), 87 - 99.e7. doi:10.1016/j.molcel.2017.11.025en_US
dc.identifier.issn1097-2765-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr1t48t-
dc.description.abstractLoss of LKB1 is associated with increased metastasis and poor prognosis in lung cancer, but the development of targeted agents is in its infancy. Here we report that a glutaminolytic enzyme, glutamate dehydrogenase 1 (GDH1), upregulated upon detachment via pleomorphic adenoma gene 1 (PLAG1), provides anti-anoikis and pro-metastatic signals in LKB1-deficient lung cancer. Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance. The effect of GDH1 on AMPK is evident in LKB1-deficient lung cancer, where AMPK activation predominantly depends on CamKK2. Targeting GDH1 with R162 attenuated tumor metastasis in patient-derived xenograft model and correlation studies in lung cancer patients further validated the clinical relevance of our finding. Our study provides insight into the molecular mechanism by which GDH1-mediated metabolic reprogramming of glutaminolysis mediates lung cancer metastasis and offers a therapeutic strategy for patients with LKB1-deficient lung cancer.en_US
dc.format.extent87 - 99.e7en_US
dc.languageengen_US
dc.language.isoen_USen_US
dc.relation.ispartofMolecular Cellen_US
dc.rightsAuthor's manuscripten_US
dc.titleThe PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer.en_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1016/j.molcel.2017.11.025-
dc.identifier.eissn1097-4164-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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