Uncoordinated 51-like kinase 2 signaling pathway regulates epithelial-mesenchymal transition in A549 lung cancer cells

Young Hwan Kim; Seung Hoon Baek; Eun Kyoung Kim; Jung Min Ha; Seo Yeon Jin; Hye Sun Lee; Hong Koo Ha; Sang Heon Song; Sun Ja Kim; Hwa Kyoung Shin; Jeongsik Yong; Do-Hyung Kim; Chi Dae Kim; Sun Sik Bae

doi:10.1002/1873-3468.12172

Uncoordinated 51-like kinase 2 signaling pathway regulates epithelial-mesenchymal transition in A549 lung cancer cells

FEBS Lett. 2016 May;590(9):1365-74. doi: 10.1002/1873-3468.12172. Epub 2016 Apr 26.

Authors

Affiliations

¹ Department of Pharmacology, Gene and Cell Therapy Center for Vessel-Associated Disease, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
² Department of Anesthesia and Pain Medicine, Pusan National University Hospital, Yangsan, Korea.
³ Department of Urology, Pusan National University Hospital, Busan, Korea.
⁴ Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.
⁵ Department of Physics, Dong-A University, Busan, Korea.
⁶ Department of Anatomy, Pusan National University School of Korean Medicine, Yangsan, Korea.
⁷ Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN, USA.

PMID: 27062295
DOI: 10.1002/1873-3468.12172

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.

Keywords: EMT; autophagy; mTORC1.

Publication types

Letter

MeSH terms

Animals
Autophagy
Autophagy-Related Protein-1 Homolog / genetics
Autophagy-Related Protein-1 Homolog / metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition*
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Mechanistic Target of Rapamycin Complex 1
Mechanistic Target of Rapamycin Complex 2
Mice
Mice, Nude
Multiprotein Complexes / genetics
Multiprotein Complexes / metabolism
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Signal Transduction*
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism

Substances

Intracellular Signaling Peptides and Proteins
Multiprotein Complexes
Autophagy-Related Protein-1 Homolog
Mechanistic Target of Rapamycin Complex 1
Mechanistic Target of Rapamycin Complex 2
Protein Serine-Threonine Kinases
TOR Serine-Threonine Kinases
ULK1 protein, human
Ulk2 protein, human