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ITGA10
α
in vivo
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NF1
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β β β
β
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in vitro in vivo
Gene expression profiles define two molecular subtypes of myxofibrosarcoma
p
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p
p
p
Silencing of integrin- 10 induces growth suppression through apoptosis in
myxofibrosarcoma cells but not in normal mesenchymal cells
ITGA10
ITGA10
Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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ITGA10
Forced expression of integrin- 10 enhances cell migration and invasion
Integrin- 10 regulates the activities of RAC/PAK and AKT in myxofibrosarcoma
Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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TRIO and RICTOR are overexpressed via DNA amplification in myxofibrosarcoma and
physically associate with integrin- 10
TRIO RICTOR
TRIO
RICTOR
RICTOR
RICTOR TRIO
RICTOR TRIO
TRIO RICTOR
ITGA10
TRIO
TRIO RICTOR
TRIO RICTOR
TRIO RICTOR
Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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TRIO and RAC are required for growth of myxofibrosarcoma cells
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RICTOR is essential for activation of AKT and cell growth for myxofibrosarcoma cells,
but not ASCs
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Constitutively active RAC, PAK, and AKT rescue ITGA10 knockdown-induced growth
suppression and apoptosis
.
Pharmacologic inhibitors of RAC and mTORC inhibit growth of myxofibrosarcoma cells
in vitro
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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mTOR inhibition sensitizes myxofibrosarcoma cells to RAC inhibitors
EHop-016 and INK128 suppress myxofibrosarcoma primary and metastatic tumor growth
in mouse xenografts
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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ITGA10
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β β
Itga10
TRIO
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in vitro
in vitro
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in vivo
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Patients
RNA isolation and microarray analysis
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Statistical Analysis
ITGA10 TRIO RICTOR
Pathway and Gene Annotation Analysis
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Copy Number Analysis
Cell Culture and Reagents
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Lentiviral transduction for shRNA and gene expression
Cell proliferation and apoptosis
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Migration and Matrigel invasion
Western Blotting
Biochemistry
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Collagen adhesion
Mouse tumorigenicity and metastasis
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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ITGA10
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α
α
α
t P
P P
TRIO RICTOR
TRIO RICTOR
Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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ITGA10
TRIO RICTOR TRIO
RICTOR
α
α
α
α
ITGA10 α
Research. on September 12, 2016. © 2016 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
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in vitro
α
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α
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p=0.0497
p=0.029p=0.043
p=0.019
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Published OnlineFirst August 30, 2016.Cancer Discov Tomoyo Okada, Ann Y. Lee, Li-Xuan Qin, et al. therapeutic targets in high-grade myxofibrosarcoma
10 dependency identifies RAC and RICTOR asαIntegrin-
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