Contribution of Soluble Factors to EMT - Cell Signal · 2018. 9. 26. · Cripto GRP78BP Smad6/7...

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For pathway key and background please visit: cellsignal.co/EMT2 Contribution of Soluble Factors to EMT Ub Ub GSK-3β Smad2 Smad3 SARA Fyn PKC Cripto GRP78BP Smad6/7 TGF-βR1 TGF-βR2 Smad1 Smad5 Smad8/9 Smad1 Smad5 Smad8/9 Smad4 Smad4 Wnt Wnt Wnt5B Wnt5A CaMKI CaMKII MMP7 MMP3 APC CK1 Axin β-Catenin WTX PP2A NICD TM NICD TM NICD TM γ-Secretase Smurf2 Smurf1 β-Catenin β-Catenin Slug Snail ZEB1/2 Twist1 GSK-3 FoxC2 Stat3 Ras Rac1 CDC42 p38 Raf JNK MEK1/2 Erk1/2 β-Catenin Transcriptional Induction of EMT Transcriptional Induction of EMT Noncanonical Wnt Signaling Canonical TGF-β Signaling Canonical Wnt Signaling Proteolytic Cleavage Jagged 1/2 Delta 1/4 Proteasomal Degradation TGF-β RTK Wnt BMP Notch Claudins Occulidins E-Cadherin Fibronectin Vitronectin N-Cadherin SPARC Integrin αV Claudins Occludins E-Cadherin Cytokeratins Fibronectin Vitronectin N-Cadherin Collagen MMPs Twist ZEB1 ZEB2 Cripto TGF-βR1 TGF-βR2 Smad2 Smad3 Expression Repression ZO-1 Cadherin Vitronectin N-Cadherins MMPs Expression Repression Expression Repression TGF-β RTK Wnt BMP Cytoplasm Nucleus Frizzled 2 Frizzled 2 Frizzled Frizzled β-Catenin PI3K PLC GSK-3β Akt BMP R T K R T K β-Catenin Sox10 NICD NICD KDM5A CSL KDM5A CSL SKIP MAML HAT Sox9 NF-κB NF-κB TGF-β 1,2,3 ADAM/TACE β-TrCP Ligand E-Cadherin Ca 2+ Actin Remodeling Stress Fiber Formation Increased Motility β-Catenin Destruction Complex TCF β-Catenin Groucho Sox9 Lef1/Tcf1 Bcl9 CBP Lef1/Tcf1 Groucho HDAC β-Catenin Notch TGF-β RTK Wnt ECM/Itg rev. 08/16/18

Transcript of Contribution of Soluble Factors to EMT - Cell Signal · 2018. 9. 26. · Cripto GRP78BP Smad6/7...

Page 1: Contribution of Soluble Factors to EMT - Cell Signal · 2018. 9. 26. · Cripto GRP78BP Smad6/7 TGF-βR1 TGF-βR2 Smad1 Smad5 Smad8/9 Smad1 ... APC CK1 Axin β enin PP2A WTX NICD

For pathway key and background please visit:

cellsignal.co/EMT2

Contribution of Soluble Factors to EMT

UbUb

GS

K-3

β

Smad2

Smad3SARA

Fyn

PKC

Cri

pto

GRP78BP

Smad6/7

TGF-

βR1

TGF-

βR2

Smad1

Smad5

Smad8/9

Smad1

Smad5

Smad8/9

Sm

ad4

Sm

ad4

Wnt

Wnt

Wnt5B Wnt5A

CaMKI

CaMKII

MMP7

MMP3

AP

C

CK

1

Axin

β-C

aten

in

WTXPP2A

NIC

DT

M

NIC

DT

M

NIC

D

TMγ-Secretase

Smurf2

Smurf1

β-Catenin

β-Catenin

SlugSnail ZEB1/2Twist1

GSK-3FoxC2

Stat3

Ras Rac1

CDC42

p38

Raf JNK

MEK1/2

Erk1/2

β-Catenin

Transcriptional Induction of EMT Transcriptional Induction of EMT

NoncanonicalWnt Signaling

Canonical TGF-βSignaling

CanonicalWnt

Signaling

Proteolytic Cleavage

Jagged 1/2Delta 1/4

Proteasomal Degradation

TGF-β RTK Wnt BMP Notch

ClaudinsOcculidinsE-Cadherin

FibronectinVitronectinN-Cadherin

SPARCIntegrin αV

ClaudinsOccludinsE-CadherinCytokeratins

FibronectinVitronectinN-CadherinCollagen

MMPsTwistZEB1ZEB2

Cri

pto

TGF-

βR1

TGF-

βR2

Smad2

Smad3

ExpressionRepressionZO-1Cadherin

VitronectinN-CadherinsMMPs

ExpressionRepressionExpressionRepression

TGF-β RTK Wnt BMP

Cytoplasm

Nucleus

Frizzled 2 Frizzled 2 Frizzled Frizzled

β-Catenin

PI3K PLC

GSK-3β

Akt

BMP

RTK

RTK

β-Catenin

Sox10NICD N

ICD

KDM5A

CSL

KDM5A

CSL SKIP

MAML

HAT

Sox9NF-κB

NF-κB

TGF-β1,2,3 ADAM/TACE

β-TrCP

Lig

and

E-Cadherin

Ca2+

Actin RemodelingStress Fiber Formation

Increased Motility

β-Catenin Destruction

Complex

TCF

β-Catenin

Groucho

Sox9Lef1/Tcf1

Bcl9

CBP

Lef1/Tcf1

Groucho

HDAC

β-Catenin

No

tch

TGF-β RTK Wnt ECM/Itg

Contribution of Soluble Factors to EMT

rev. 08/16/18

Page 2: Contribution of Soluble Factors to EMT - Cell Signal · 2018. 9. 26. · Cripto GRP78BP Smad6/7 TGF-βR1 TGF-βR2 Smad1 Smad5 Smad8/9 Smad1 ... APC CK1 Axin β enin PP2A WTX NICD

For pathway key and background please visit:

APPLICATIONS & REACTIVITY KEY: WB Western Blotting / IP Immunoprecipitation / IHC Immunohistochemistry / IF Immunofluorescence / F Flow Cytometry / ChIP Chromatin Immunoprecipitation / -IC Immunocytochemistry / -P Paraffin / -F Frozen / E-P Peptide ELISA / H human / M mouse / R rat / Hm hamster / Mk monkey / C chicken / Mi mink / Dm D. melanogaster / X Xenopus / Z zebrafish / B bovine / Dg dog / Pg pig / Sc S. cerevisiae / All all species expected / ( ) 100% sequence homology

18-C

EL-1

2815

-FLY

2-E1

For R

esea

rch

Use

Only

. Not

For

Use

In D

iagn

ostic

Pro

cedu

res.

cellsignal.co/EMT2

© 2018 Cell Signaling Technology, Inc. Cell Signaling Technology, CST, and XP are trademarks of Cell Signaling Technology, Inc. U.S. Patent No. 5,675,063. All other trademarks are the property of their respective owners.

Key Products for the Contribution of Soluble Factors to EMTVisit www.cellsignal.com for a full listing of antibodies, related kits, and reagents.

ANTIBODIES & KITS APPLICATIONS REACTIVITY

#4147 Cleaved Notch1 (Val1744) (D3B8) Rabbit mAb WB, IP, ChIP H, M, R

#8658 Notch Receptor Interaction Antibody Sampler Kit

#2041 PP2A A Subunit (81G5) Rabbit mAb WB, IHC-P, IF-IC H, M, R, Mk

#4953 PP2A B Subunit Antibody WB, IP, IHC-P, IF-IC, F H,M, R, Mk, (C)

#2038 PP2A C Subunit Antibody WB, IP, IHC-P, IF-IC, F H, M, R, Mk, Dm, (C, Pg)

#5313 RBPSUH (D10A4) XP® Rabbit mAb WB, IHC-P, ChIP H, M, R, Mk

#9585 Slug (C19G7) Rabbit mAb WB, IP, IF-IC, F H, M

#6944 Smad1 (D59D7) XP® Rabbit mAb WB, IP, ChIP H, M, Mk, (X, B)

#13820 Phospho-Smad1 (Ser463/465)/Smad5 (Ser463/465)/Smad9 (Ser465/467) (D5B10) Rabbit mAb

WB, IP, IF-IC, F H, M, R, (Mk)

#12656 Smad 1/5/9 Antibody Sampler Kit

#5339 Smad2 (D43B4) XP® Rabbit mAb WB, IP, IF-IC, F, ChIP H, M, R, Mk

#18338 Phospho-SMAD2 (Ser465/Ser467) (E8F3R) Rabbit mAb

WB, IP, IF-IC, F, ChIP H, M, R

#8685 Smad2/3 (D7G7) XP® Rabbit mAb WB, IP, IF-IC, F, ChIP, ChIP-seq

H, M, R, Mk

#12747 Smad2/3 Antibody Sampler Kit

#9523 Smad3 (C67H9) Rabbit mAb WB, IP, IF-IC, F, ChIP,ChIP-seq

H, M, R, Mk, (X, Z, B)

#46535 SMAD4 (D3R4N) XP® Rabbit mAb WB, IP, IHC-P, IF-IC, F, ChIP, ChIP-seq

H, M, R, Mk

#12534 Smad5 (D4G2) Rabbit mAb WB, IP, ChIP H, M, R, Mk

#3879 Snail (C15D3) Rabbit mAb WB, IP H, M, R, Mk

#82630 Sox9 (D8G8H) Rabbit mAb WB, IHC-P, IF-IC, F H, (M, R)

#89356 Sox10 (D5V9L) Rabbit mAb WB, IP, IF-IC H

#3976 TACE Antibody WB, IP H, Mk

#3396 TCF8/ZEB1 (D80D3) Rabbit mAb WB, IP H, (M, R)

#3711 TGF-ß Antibody WB H, M, R

#79424 TGF-ß Receptor II Antibody WB H, M, R

#46702 TWIST1 Antibody WB, IP H

#2721 Wnt3a (C64F2) Rabbit mAb WB, IP M, (H, R)

#2530 Wnt5a/b (C27E8) Rabbit mAb WB H

Jagged1 (D4Y1R) XP® Rabbit mAb #70109 Flow cytometric analysis of Jurkat cells (blue) and MKN45 cells (green) using #70109. Anti-rabbit IgG (H+L), F(ab’)2 Fragment (Alexa Fluor® 488 Conjugate) #4412 was used as a secondary antibody.

Jagged1

Even

ts

SMAD4 (D3R4N) XP® Rabbit mAb #46535 IHC analysis of paraffin-embedded human prostate carcinoma using #46535.

ANTIBODIES & KITS APPLICATIONS REACTIVITY

#4151 ADAM9 (D64B5) Rabbit mAb WB H, M, R, Mk

#2504 APC Antibody WB, IP H, (M, R,Mk)

#2087 Axin1 (C76H11) Rabbit mAb WB, IP, IHC-P H, M

#2151 Axin2 (76G6) Rabbit mAb WB, IP H

#13116 N-Cadherin (D4R1H) XP® Rabbit mAb WB, IP, IHC-P, IF-IC H, M

#4436 CaMKII (pan) (D11A10) Rabbit mAb WB H, M, R

#9561 Phospho-ß-Catenin (Ser33/37/Thr41) Antibody

WB H, M, R, Mk, (C, X, Z, B, Dg, Pg)

#4176 Phospho-ß-Catenin (Ser675) (D2F1) XP® Rabbit mAb

WB, IP, IF-F, IF-IC H, M, R, (M, R, C X, Z)

#7389 CBP (D6C5) Rabbit mAb WB, IP, IF-IC, ChIP, ChIP-seq

H, M, R, Mk

#2466 Cdc42 (11A11) Rabbit mAb WB H, M, R, B, (X)

#2655 CK1 Antibody WB H, M, R, (C, X, Z, B)

#96406 DLL4 (D7N3H) Rabbit mAb WB, IP, IF-IC H

#4023 Fyn Antibody WB H, M

#70109 Jagged1 (D4Y1R) XP® Rabbit mAb WB, IP, IHC-P, F H, M, Mk, (R, Hm)

#2210 Jagged2 (C23D2) Rabbit mAb WB, IP H, R

#3876 JARID1A (D28B10) Rabbit mAb WB, IP H, M, (R, B)

#25807 Keratin 5 (D4U8Q) Rabbit mAb WB, IF-IC, F H

#4465 Keratin 7 (D1E4) XP® Rabbit mAb WB, IF-IC, F H

#4546 Keratin 8/18 (C51) Mouse mAb WB, IHC-P, IF-IC F H, Mk

#12434 Keratin 17/19 (D4G2) XP® Rabbit mAb WB, IHC-P, IF-IC H, M, R

#4548 Keratin 18 (DC10) Mouse mAb WB, IHC-P, IF-IC,F H

#4558 Keratin 19 (BA17) Mouse mAb WB, IHC-P H

#13063 Keratin 20 (D9Z1Z) XP® Rabbit mAb WB, IHC-P, IF-IC, F H

#4545 Pan-Keratin (C11) Mouse mAb WB, IHC-P, IF-P, IF-IC, F H, M, R, Mk

#12166 MAML1 (D3K7B) Rabbit mAb WB IP, ChIP, ChIP-seq H, M, R

#6988 MAML2 (D41E6) Rabbit mAb WB, IP H, M, R

#8242 NF-κB p65 (D14E12) XP® Rabbit mAb WB, IP, IHC-P, IF-IC, F, ChIP, ChIP-seq

H, M, R, Hm, Mk, Dg

#3608 Notch1 (D1E11) XP® Rabbit mAb WB, IP, IHC-P, ChIP H, M, R

#5732 Notch2 (D76A6) XP® Rabbit mAb WB, IP, IF-IC, F H, M, R

Slug (C19G7) Rabbit mAb #9585 Confocal IF analysis of A204 cells (left) and PANC-1 cells (right) using #9585. Actin filaments have been labeled with DY554 phalloidin (red).

Snail (C15D3) Rabbit mAb #3879 WB analysis of extracts from various cell lines using #3879.

kDa

Snail

200

140

100

80

6050

40

30

20

HC T116

HeLa

NIH/3T

3

Rat2 COS-7