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Snail acetylation by autophagy-derived acetyl-coenzyme A promotes invasion and metastasis of KRAS-LKB1 co-mutated lung cancer cells

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Cancer Communications 2022年第8期42卷 716-749页

作者： Jang Hee Han Yong Keon kim Hakhyun kim Jooyoung Lee Myung Joon Oh Sang Bum kim minjee kim Kook Hwan kim Hyun Ju Yoon Myung-Shik Lee John D.Minna Michael A.White Hyun Seok kim Severance Biomedical Science Institute Yonsei University College of MedicineSeoul 03722Korea Department of Medical Science Yonsei University Graduate SchoolSeoul 03722Korea Department of Urology Seoul National University HospitalSeoul 03722Korea Checkmate Therapeutics Inc. Seoul 07207Korea Hamon Center for Therapeutic Oncology Research University of Texas Southwestern Medical CenterDallasTexas 75390USA Department of Cell Biology University of Texas Southwestern Medical CenterDallasTexas 75390USA Graduate School of Medical Science Brain Korea 21 ProjectYonsei University College of MedicineSeoul 03722Korea

Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates ***: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging ***: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target o

关键词： snail autophagy acetyl-coenzyme A epithelial-to-mesenchymal transition non-small-cell lung cancer CAMKK2 acetyl-snail pancreatic cancer KRAS inhibitor metastasis ACLY

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Anti-inflammatory Activity of the Extract of Inula helenium on Skeletal Muscle Cell

Anti-inflammatory Activity of the Extract of Inula helenium ...

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第十四届全国中药和天然药物学术研讨会

作者： minjee kim Jaemoo Chun Kyoung Jin Lee Yeong Shik kim Seoul National University

＜正＞Muscle damage due to exercise,sprains and strains causes inflammation and can lead to various functional *** root of Inula helenium was traditionally used as a folk medicine against various inflammatory *** sesquiterpene lactone of its extracted compounds belong to the same family that of Arnica montana,European traditional remedy for muscle

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