PMID- 29481833
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20180920
IS  - 0167-4889 (Print)
IS  - 0167-4889 (Linking)
VI  - 1865
IP  - 5
DP  - 2018 May
TI  - Autophagy modulates transforming growth factor beta 1 induced epithelial to 
      mesenchymal transition in non-small cell lung cancer cells.
PG  - 749-768
LID - S0167-4889(18)30031-4 [pii]
LID - 10.1016/j.bbamcr.2018.02.007 [doi]
AB  - Lung cancer is considered one of the most frequent causes of cancer-related death 
      worldwide and Non-Small Cell Lung Cancer (NSCLC) accounts for 80% of all lung 
      cancer cases. Autophagy is a cellular process responsible for the recycling of 
      damaged organelles and protein aggregates. Transforming growth factor beta-1 
      (TGFbeta(1)) is involved in Epithelial to Mesenchymal Transition (EMT) and autophagy 
      induction in different cancer models and plays an important role in the 
      pathogenesis of NSCLC. It is not clear how autophagy can regulate EMT in NSCLC 
      cells. In the present study, we have investigated the regulatory role of 
      autophagy in EMT induction in NSCLC and show that TGFbeta(1) can simultaneously 
      induce both autophagy and EMT in the NSCL lines A549 and H1975. Upon chemical 
      inhibition of autophagy using Bafilomycin-A1, the expression of the mesenchymal 
      marker vimentin and N-cadherin was reduced. Immunoblotting and 
      immunocytochemistry (ICC) showed that the mesenchymal marker vimentin was 
      significantly downregulated upon TGFbeta(1) treatment in ATG7 knockdown cells when 
      compared to corresponding cells treated with scramble shRNA (negative control), 
      while E-cadherin was unchanged. Furthermore, autophagy inhibition (Bafilomycin A1 
      and ATG7 knockdown) decreased two important mesenchymal functions, migration and 
      contraction, of NSCLC cells upon TGFbeta(1) treatment. This study identified a 
      crucial role of autophagy as a potential positive regulator of TGFbeta(1)-induced 
      EMT in NSCLC cells and identifies inhibitors of autophagy as promising new drugs 
      in antagonizing the role of EMT inducers, like TGFbeta(1), in the clinical 
      progression of NSCLC.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Alizadeh, Javad
AU  - Alizadeh J
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
FAU - Glogowska, Aleksandra
AU  - Glogowska A
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
FAU - Thliveris, James
AU  - Thliveris J
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
FAU - Kalantari, Forouh
AU  - Kalantari F
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
FAU - Shojaei, Shahla
AU  - Shojaei S
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
FAU - Hombach-Klonisch, Sabine
AU  - Hombach-Klonisch S
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
FAU - Klonisch, Thomas
AU  - Klonisch T
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Surgery, 
      Max Rady College of Medicine, Rady Faculty of Health Sciences, University of 
      Manitoba, Winnipeg, Canada; Medical Microbiology & Infectious Diseases, Max Rady 
      College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 
      Winnipeg, Canada.
FAU - Ghavami, Saeid
AU  - Ghavami S
AD  - Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady 
      Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Biology of 
      Breathing Theme, Children's Hospital Research Institute of Manitoba, University 
      of Manitoba, Winnipeg, Canada; Health Policy Research Center, Institute of 
      Health, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: 
      saeid.ghavami@umanitoba.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180224
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Res
JT  - Biochimica et biophysica acta. Molecular cell research
JID - 101731731
RN  - 0 (Cadherins)
RN  - 0 (Macrolides)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Vimentin)
RN  - 88899-56-3 (bafilomycin B1)
SB  - IM
MH  - A549 Cells
MH  - Autophagy/drug effects/*genetics
MH  - Cadherins/genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Macrolides/administration & dosage
MH  - Transforming Growth Factor beta1/*genetics
MH  - Vimentin/genetics
OTO - NOTNLM
OT  - Autophagy
OT  - Cellular phenotype conversion
OT  - Cellular stress
OT  - Lung cancer
OT  - Lung epithelial cells
EDAT- 2018/02/27 06:00
MHDA- 2018/07/10 06:00
CRDT- 2018/02/27 06:00
PHST- 2017/11/08 00:00 [received]
PHST- 2018/02/15 00:00 [revised]
PHST- 2018/02/18 00:00 [accepted]
PHST- 2018/02/27 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2018/02/27 06:00 [entrez]
AID - S0167-4889(18)30031-4 [pii]
AID - 10.1016/j.bbamcr.2018.02.007 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Res. 2018 May;1865(5):749-768. doi: 
      10.1016/j.bbamcr.2018.02.007. Epub 2018 Feb 24.