title: Uncoordinated 51-like kinase 2 signaling pathway regulates epithelial-mesenchymal transition in A549 lung cancer cells.
abstract: Epithelial-mesenchymal transition (EMT) is a critical response during cancer cell metastasis. In this study, we provide evidence that uncoordinated 51-like kinase 2 (ULK2) regulates EMT. Induction of autophagy by inhibition of mammalian target of rapamycin complex 1 (mTORC1) or by disruption of mTORC1 by silencing raptor significantly enhanced EMT, however, disruption of mTORC2 by silencing rictor had no effect. Knockdown of ULK2 expression significantly induced autophagy, EMT, and migration but suppressed proliferation as well as tumor growth in a xenotransplantation model, whereas silencing of ULK1 had no effect. Therefore, we suggest that ULK2 regulates EMT through modulation of autophagy.
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University Hospital, Yangsan, Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Urology, Pusan National University Hospital, Busan, Korea.
authors.forename: Hong Koo
authors.initials: HK
authors.lastname: Ha
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Physics, Dong-A University, Busan, Korea.
authors.forename: Sun Ja
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Pusan National University School of Korean Medicine, Yangsan, Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN, USA.
authors.forename: Jeongsik
authors.initials: J
authors.lastname: Yong
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN, USA.
authors.forename: Do-Hyung
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008819:Mice, Nude; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000071189:Autophagy-Related Protein-1 Homolog; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C484754:ULK1 protein, human; C541703:Ulk2 protein, human
keywords: EMT; autophagy; mTORC1