PMID- 28778674
OWN - NLM
STAT- MEDLINE
DCOM- 20171113
LR  - 20180206
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 90
DP  - 2017 Sep
TI  - Calreticulin regulates TGF-beta1-induced epithelial mesenchymal transition through 
      modulating Smad signaling and calcium signaling.
PG  - 103-113
LID - S1357-2725(17)30186-3 [pii]
LID - 10.1016/j.biocel.2017.07.023 [doi]
AB  - As a Ca(2+) binding protein, calreticulin (CRT) has many functions and plays an 
      important role in a variety of tumors. The role of CRT in TGF-beta1-induced EMT is 
      unknown. In this study, we demonstrated in vitro that TGF-beta1-induced EMT elevated 
      the expression of CRT in A549 lung cancer cells. Subsequently, we confirmed that 
      overexpression CRT had no capacity to induce A549 cells EMT alone, but 
      successfully enhanced TGF-beta1-induced-EMT. Furthermore, knockdown of CRT in A549 
      cells significantly suppressed changes of EMT marks expression induced by TGF-beta1. 
      On treatment with TGF-beta1, overexpression of CRT could enhance the phosphorylation 
      of both Smad2 and Smad3. Consistently, the knockdown of CRT by siRNA-CRT could 
      inhibit Smad signaling pathway activated by TGF-beta1. These results indicated that 
      CRT regulates EMT induced by TGF-beta1 through Smad signaling pathway. Finally, 
      TGF-beta1-induced-EMT enhanced store-operated Ca(2+) influx in A549 cells. CRT 
      knockdown was able to abolish the effect of TGF-beta1 on thapsigargin (TG) -induced 
      Ca(2+) release, but had failed to reduce store-operated Ca(2+) influx. The 
      alteration of intracellular Ca(2+) concentration by TG or BAPTA-AM was able to 
      regulate EMT induced by TGF-beta1 through Smad signaling pathway. Together, these 
      data identify that CRT regulates TGF-beta1-induced-EMT through modulating Smad 
      signaling. Furthermore, TGF-beta1-induced-EMT is highly calcium-dependent, CRT was 
      partly involved in it.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Wu, Yanjiao
AU  - Wu Y
AD  - Key Laboratory of Biorheological Science and Technology, Ministry of Education, 
      College of Bioengineering, Chongqing University, Chongqing, 400044, China.
FAU - Xu, Xiaoli
AU  - Xu X
AD  - Key Laboratory of Biorheological Science and Technology, Ministry of Education, 
      College of Bioengineering, Chongqing University, Chongqing, 400044, China.
FAU - Ma, Lunkun
AU  - Ma L
AD  - Key Laboratory of Biorheological Science and Technology, Ministry of Education, 
      College of Bioengineering, Chongqing University, Chongqing, 400044, China.
FAU - Yi, Qian
AU  - Yi Q
AD  - Key Laboratory of Biorheological Science and Technology, Ministry of Education, 
      College of Bioengineering, Chongqing University, Chongqing, 400044, China; State 
      Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and 
      the Ministry of Science and Technology, College of Biomedical Engineering, 
      Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, 
      Chongqing, 400016, China.
FAU - Sun, Weichao
AU  - Sun W
AD  - Key Laboratory of Biorheological Science and Technology, Ministry of Education, 
      College of Bioengineering, Chongqing University, Chongqing, 400044, China.
FAU - Tang, Liling
AU  - Tang L
AD  - Key Laboratory of Biorheological Science and Technology, Ministry of Education, 
      College of Bioengineering, Chongqing University, Chongqing, 400044, China. 
      Electronic address: tangliling@cqu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170801
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Calreticulin)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta1)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Biological Transport/drug effects
MH  - Calcium/metabolism
MH  - Calcium Signaling/*drug effects
MH  - Calreticulin/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Smad2 Protein/*metabolism
MH  - Smad3 Protein/*metabolism
MH  - Transforming Growth Factor beta1/*pharmacology
OTO - NOTNLM
OT  - Calcium signaling
OT  - Calreticulin
OT  - EMT
OT  - Smad signaling
OT  - TGF-beta1
EDAT- 2017/08/06 06:00
MHDA- 2017/11/14 06:00
CRDT- 2017/08/06 06:00
PHST- 2017/04/28 00:00 [received]
PHST- 2017/07/22 00:00 [revised]
PHST- 2017/07/31 00:00 [accepted]
PHST- 2017/08/06 06:00 [pubmed]
PHST- 2017/11/14 06:00 [medline]
PHST- 2017/08/06 06:00 [entrez]
AID - S1357-2725(17)30186-3 [pii]
AID - 10.1016/j.biocel.2017.07.023 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2017 Sep;90:103-113. doi: 10.1016/j.biocel.2017.07.023. 
      Epub 2017 Aug 1.