PMID- 25761241
OWN - NLM
STAT- MEDLINE
DCOM- 20151125
LR  - 20211203
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 16
IP  - 3
DP  - 2015 Mar 9
TI  - Tetraspanin 8-rictor-integrin alpha3 complex is required for glioma cell migration.
PG  - 5363-74
LID - 10.3390/ijms16035363 [doi]
AB  - The malignant glioma remains one of the most aggressive human malignancies with 
      extremely poor prognosis. Glioma cell invasion and migration are the main causes 
      of death. In the current study, we studied the expression and the potential 
      functions of tetraspanin 8 (Tspan8) in malignant gliomas. We found that Tspan8 
      expression level is high in both malignant glioma tissues and in several human 
      glioma cell lines, where it formed a complex integrin alpha3 and rictor, the latter 
      is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2). 
      Disruption of this complex, through siRNA-mediated knockdown of anyone of these 
      three proteins, inhibited U251MG glioma cell migration in vitro. We further 
      showed that Tspan8-rictor association appeared required for mTORC2 activation. 
      Knockdown of Tspan8 by the targeted siRNAs prevented mTOR-rictor (mTORC2) 
      assembly as well as phosphorylation of AKT (Ser-473) and protein kinase C alpha 
      (PKCalpha) in U251MG cells. Together, these results demonstrate that over-expressed 
      Tspan8 in malignant glioma forms a complex with rictor and integrin alpha3 to mediate 
      mTORC2 activation and glioma cell migration. Therefore, targeting 
      Tspan8-rictor-integrin alpha3 complex may provide a potential therapeutic 
      intervention for malignant glioma.
FAU - Pan, Si-Jian
AU  - Pan SJ
AD  - Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao 
      Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. 
      pansijian163@163.com.
FAU - Zhan, Shi-Kun
AU  - Zhan SK
AD  - Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School 
      of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, 
      Shanghai 200025, China. shikun_zhan@163.com.
FAU - Pan, Yi-Xin
AU  - Pan YX
AD  - Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School 
      of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, 
      Shanghai 200025, China. yixinpan@163.com.
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School 
      of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, 
      Shanghai 200025, China. doctorliuwei@163.com.
FAU - Bian, Liu-Guan
AU  - Bian LG
AD  - Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao 
      Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. 
      blg11118@rjh.com.cn.
FAU - Sun, Bomin
AU  - Sun B
AD  - Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School 
      of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, 
      Shanghai 200025, China. bomin_sun@163.com.
FAU - Sun, Qing-Fang
AU  - Sun QF
AD  - Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao 
      Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China. 
      sunqingfang11@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150309
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Carrier Proteins)
RN  - 0 (Integrin alpha3)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (RICTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (TSPAN8 protein, human)
RN  - 0 (Tetraspanins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - *Cell Movement
MH  - Glioma/*metabolism/pathology
MH  - Humans
MH  - Integrin alpha3/genetics/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Multiprotein Complexes/genetics/metabolism
MH  - Protein Binding
MH  - Protein Kinase C/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Tetraspanins/genetics/*metabolism
PMC - PMC4394480
EDAT- 2015/03/12 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/03/01
CRDT- 2015/03/12 06:00
PHST- 2015/01/05 00:00 [received]
PHST- 2015/02/03 00:00 [revised]
PHST- 2015/02/09 00:00 [accepted]
PHST- 2015/03/12 06:00 [entrez]
PHST- 2015/03/12 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - ijms16035363 [pii]
AID - ijms-16-05363 [pii]
AID - 10.3390/ijms16035363 [doi]
PST - epublish
SO  - Int J Mol Sci. 2015 Mar 9;16(3):5363-74. doi: 10.3390/ijms16035363.