PMID- 30394687
OWN - NLM
STAT- MEDLINE
DCOM- 20200611
LR  - 20210503
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 23
IP  - 1
DP  - 2019 Jan
TI  - CPT1A-mediated succinylation of S100A10 increases human gastric cancer invasion.
PG  - 293-305
LID - 10.1111/jcmm.13920 [doi]
AB  - Gastric cancer (GC) is a malignancy of the lining of the stomach and is prone to 
      distant metastasis, which involves a variety of complex molecules. The S100 
      proteins are a family of calcium-binding cytosolic proteins that possess a wide 
      range of intracellular and extracellular functions and play pivotal roles in the 
      invasion and migration of tumour cells. Among these, S100A10 is known to be 
      overexpressed in GC. Lysine succinylation, a recently identified form of protein 
      post-translational modification, is an important regulator of cellular processes. 
      Here, we demonstrated that S100A10 was succinylated at lysine residue 47 (K47), 
      and levels of succinylated S100A10 were increased in human GC. Moreover, K47 
      succinylation of S100A10 was stabilized by suppression of ubiquitylation and 
      subsequent proteasomal degradation. Furthermore, carnitine palmitoyltransferase 
      1A (CPT1A) was found to function as a lysine succinyltransferase that interacts 
      with S100A10. Succinylation of S100A10 is regulated by CPT1A, while 
      desuccinylation is regulated by SIRT5. Overexpression of a succinylation mimetic 
      mutant, K47E S100A10, increased cell invasion and migration. Taken together, this 
      study reveals a novel mechanism of S100A10 accumulation mediated by succinylation 
      in GC, which promotes GC progression and is regulated by the succinyltransferase 
      CPT1A and SIRT5-mediated desuccinylation.
CI  - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Wang, Chao
AU  - Wang C
AD  - Department of Surgery, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Zhang, Chen
AU  - Zhang C
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Li, Xiang
AU  - Li X
AD  - Department of Surgery, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Shen, Jiajia
AU  - Shen J
AD  - Department of Surgery, First Affiliated Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Xu, Yue
AU  - Xu Y
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Shi, Hui
AU  - Shi H
AD  - Department of Thoracic Surgery, Affiliated Hospital of Nantong University, 
      Nantong, Jiangsu, China.
FAU - Mu, Xianmin
AU  - Mu X
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Pan, Jinshun
AU  - Pan J
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Zhao, Ting
AU  - Zhao T
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Li, Mengjing
AU  - Li M
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Geng, Biao
AU  - Geng B
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Xu, Che
AU  - Xu C
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - Wen, Hao
AU  - Wen H
AD  - Department of Surgery, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
FAU - You, Qiang
AU  - You Q
AUID- ORCID: 0000-0003-3308-4127
AD  - Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, China.
AD  - Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing 
      Medical University, Nanjing, Jiangsu, China.
AD  - Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, Jiangsu, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181105
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Annexin A2)
RN  - 0 (S100 Proteins)
RN  - 0 (S100 calcium binding protein A10)
RN  - 0 (Succinates)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 3.5.1.- (SIRT5 protein, human)
RN  - EC 3.5.1.- (Sirtuins)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Annexin A2/genetics/*metabolism
MH  - Carnitine O-Palmitoyltransferase/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/pathology/secondary
MH  - Lysine/metabolism
MH  - Male
MH  - Melanoma, Experimental/pathology
MH  - Mice, Inbred C57BL
MH  - Protein Processing, Post-Translational
MH  - S100 Proteins/genetics/*metabolism
MH  - Sirtuins/metabolism
MH  - Stomach Neoplasms/metabolism/*pathology
MH  - Succinates/metabolism
PMC - PMC6307794
OTO - NOTNLM
OT  - CPT1A
OT  - S100A10
OT  - SIRT5
OT  - gastric cancer
OT  - metastasis
OT  - succinylation
OT  - ubiquitylation
EDAT- 2018/11/06 06:00
MHDA- 2020/06/12 06:00
PMCR- 2019/01/01
CRDT- 2018/11/06 06:00
PHST- 2018/05/18 00:00 [received]
PHST- 2018/07/31 00:00 [revised]
PHST- 2018/08/26 00:00 [accepted]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2020/06/12 06:00 [medline]
PHST- 2018/11/06 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - JCMM13920 [pii]
AID - 10.1111/jcmm.13920 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2019 Jan;23(1):293-305. doi: 10.1111/jcmm.13920. Epub 2018 Nov 5.