PMID- 33237393
OWN - NLM
STAT- MEDLINE
DCOM- 20211005
LR  - 20211126
IS  - 1995-820X (Electronic)
IS  - 1674-0769 (Print)
IS  - 1995-820X (Linking)
VI  - 36
IP  - 3
DP  - 2021 Jun
TI  - Tumor Necrosis Factor alpha Reduces SNAP29 Dependent Autolysosome Formation to 
      Increase Prion Protein Level and Promote Tumor Cell Migration.
PG  - 458-475
LID - 10.1007/s12250-020-00320-4 [doi]
AB  - Tumor Necrosis Factor alpha (TNFalpha) is best known as a mediator of inflammation and 
      immunity, and also plays important roles in tumor biology. However, the role of 
      TNFalpha in tumor biology is complex and not completely understood. In a human 
      melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFalpha up-regulates 
      prion protein (PrP) level, and promotes tumor cell migration in a PrP dependent 
      manner. Silencing PRNP abrogates TNFalpha induced tumor cell migration; this 
      phenotype is reversed when PRNP is re-introduced. Treatment with TNFalpha activates 
      nuclear factor kappa B (NF-kappaB) signaling, which then mitigates autophagy by 
      reducing the expression of Forkhead Box P3 (FOXP3). Down regulation of FOXP3 
      reduces the transcription of synaptosome associated protein 29 (SNAP29), which is 
      essential in the fusion of autophagosome and lysosome creating autolysosome. 
      FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a 
      promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also 
      up-regulates PrP, and promotes tumor cell migration without TNFalpha treatment. But, 
      when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to 
      TNFalpha. Thus, a reduction in autophagy is the underlying mechanism by which 
      expression of PrP is up-regulated, and tumor cell migration is enhanced upon TNFalpha 
      treatment. Disrupting the TNFalpha-NF-kappaB-FOXP3-SNAP29 signaling axis may provide a 
      therapeutic approach to mitigate tumor cell migration.
FAU - Li, Huan
AU  - Li H
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100000, China.
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China.
FAU - Wang, Ren
AU  - Wang R
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China.
FAU - Yu, Ze
AU  - Yu Z
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China.
FAU - Shi, Run
AU  - Shi R
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Department of Stomatology, First Affiliated Hospital, School of Medicine, Shihezi 
      University, Shihezi, 832008, China.
FAU - Gao, Shanshan
AU  - Gao S
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
FAU - Shao, Ming
AU  - Shao M
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
FAU - Cui, Shuzhong
AU  - Cui S
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China.
AD  - Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical 
      University, Guangzhou, 510095, China.
FAU - Gao, Zhenxing
AU  - Gao Z
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China.
FAU - Xu, Jiang
AU  - Xu J
AD  - Department of Stomatology, First Affiliated Hospital, School of Medicine, Shihezi 
      University, Shihezi, 832008, China.
FAU - Sy, Man-Sun
AU  - Sy MS
AD  - Department of Pathology, School of Medicine, Case Western Reserve University, 
      Cleveland, OH, 44106, USA.
FAU - Li, Chaoyang
AU  - Li C
AUID- ORCID: 0000-0003-3582-4141
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. 
      chaoyangli@gzhmu.edu.cn.
AD  - Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State 
      Key Laboratory of Respiratory Disease, Guangzhou, 510095, China. 
      chaoyangli@gzhmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20201125
PL  - Netherlands
TA  - Virol Sin
JT  - Virologica Sinica
JID - 101514185
RN  - 0 (NF-kappa B)
RN  - 0 (Prion Proteins)
RN  - 0 (Prions)
RN  - 0 (Qb-SNARE Proteins)
RN  - 0 (Qc-SNARE Proteins)
RN  - 0 (Snap29 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cell Movement
MH  - Lysosomes
MH  - Mice
MH  - NF-kappa B
MH  - Prion Proteins/genetics
MH  - *Prions
MH  - Qb-SNARE Proteins
MH  - Qc-SNARE Proteins
MH  - *Tumor Necrosis Factor-alpha
PMC - PMC8257879
OTO - NOTNLM
OT  - Autophagy
OT  - Forkhead box P3 (FOXP3)
OT  - Nuclear factor kappa B (NF-kappaB)
OT  - Prion protein
OT  - Synaptosome associated protein 29 (SNAP29)
OT  - Tumor necrosis factor alpha (TNFalpha)
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article.
EDAT- 2020/11/26 06:00
MHDA- 2021/10/06 06:00
PMCR- 2021/11/25
CRDT- 2020/11/25 12:17
PHST- 2020/08/12 00:00 [received]
PHST- 2020/10/10 00:00 [accepted]
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2021/10/06 06:00 [medline]
PHST- 2020/11/25 12:17 [entrez]
PHST- 2021/11/25 00:00 [pmc-release]
AID - 10.1007/s12250-020-00320-4 [pii]
AID - 320 [pii]
AID - 10.1007/s12250-020-00320-4 [doi]
PST - ppublish
SO  - Virol Sin. 2021 Jun;36(3):458-475. doi: 10.1007/s12250-020-00320-4. Epub 2020 Nov 
      25.