TROP2 regulatory signaling (Homo sapiens)

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Up-regulationProteinmRNAProteinmRNAProteinmRNA Down-regulationProtein Components of complex unknownCa2+ Calcium ionProteinProtein Proteins in complexProteinXXXX Proteins with/without phosphositeFACECYNUTROP2-ICD TROP2 intracellular domain Protein-protein interaction Kinase-substrate reaction Leads to through unknown mechanisms or indication of studied cell types Leads to decrease in activity or phosphorylation at sites Translocation of proteins Transcriptional or translational regulation of gene/protein expression Cytoplasm Cell leading edges Focal adhesions NucleusLegend19TACSTD2243, 8208111, 27263733TROP2 prevents IGF1 & MDKbinding to IGF1R &ALK, respectively, bycompetitive bindingIn LNCaP cells and xenograftsleading toDNA condensationand decrease inhistone methylationInHUVECsIntracellular(TROP2-ICD)InMTE-4-14 cellsIn GBC-SD andSGC-996 cellsTROP2dimerInHCT116cellsEnhancesGC cell tolerance tochemotherapyEnhanceddirectionalmigrationIn the leading edges of prostate cancer cells plated on FN 24, 31Ca2+CLDN1CLDN712PARP1CD56PSMAPSASOX2MYCTP63OCT3/4ARUpregulatedin VCaP cells &downregulatedin LNCaP cells& 22Rv1 cells SYPInLNCaPandPC-3cells 1212ABCC1NOTCH1In BGC-823 andHGC27 cells 3939393916CDKN2A16Cell cycleregulation16PRKAA216PIK3R1PAKT1T308S47344, 7, 97Proliferation and migrationof HN6, SCC4,MG63, KM12SMMNNG/HOS, U2OS,MTE4-14 andPC-9/GR cells4, 7, 25MMP2In 8505C,K1 andFT-133 cells5AP155, 33MAPK8MAPK9Y185T183Y185T183MAPK1MAPK3Y187T185Y204T2025, 14, 23, 27, 3755PTENS380PDPK19999IGF119, 4119, 41MDK411515, 26PRKCAPRKCD26CASP337In A549NSCLCs37MMP1337PECAM1EGFRY1173In A549NSCLCs37ACVRL1IGF1RY1604Y1151Y1150Y1135Y11364141414114, 41InHeLacells4141RAC1GTP88ITGB1ITGA53, 8TLN1TLN1814, 27CREB1S133STAT1Y701RB1S780NFKB133SRCPTK2Y416Y397InPC3-2cellsJUNIn FT-133,FADU andMTE-4-14 cellsADAM10 29TACSTD2S32238CDH1Affinity:CLDN7>CLDN1BCL230, 35BAXInA2780,Hela and C33AcellsCTNNB11, 23FN1VIMCDH1Induces EMTin MGC803cells23, 30CDK4InHelaandC33Acells23In LNCaP &TRAMP C2 cells22CCND1CCNE1CDK2CDKN1BInPanc02, Hela and C33AcellsJAK2Y1008STAT3Y1007S727Y705666In LN-229and U87-MGcellsPSEN2ADAM17 2020TACSTD2TROP2-ICD20PSEN1 ADAM17 202, 20In LNCaPcells 2020223030Upregulatedin Panc02, Hela,C33ATRAMP C2 &HEP2 cells anddown-regulatedin MTE-4-14 cells1212121212InLNCaP,PC-3,VCaP,DU-145cellsIn LNCaP cells and xenografts,PC-3, andVCaP cells1212121212CTNNB11191919In TROP2-overexpressingH1299,CL1-0and H23 lungcancer cellsIn TROP2-overexpressingH1299,CL1-0and H23 lungcancer cells1919InH1299 andH23 cellsIGF2RIGF225252525RACK133333393314, 271214CYNUCYNUFACEIn MTE-4-14 cells141414, 2737 TROP2 regulatory signaling networkPAK4S4748820NUMBIn v-SRC PECcells 209


Description

Schematic representation of TROP2 mediated signaling mechanism in different types of cancers

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Bibliography

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  15. Nakatsukasa M, Kawasaki S, Yamasaki K, Fukuoka H, Matsuda A, Tsujikawa M, Tanioka H, Nagata-Takaoka M, Hamuro J, Kinoshita S; ''Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: implications in the pathogenesis of gelatinous drop-like corneal dystrophy.''; Am J Pathol, 2010 PubMed Europe PMC Scholia
  16. Jia L, Wang T, Ding G, Kuai X, Wang X, Wang B, Zhao W, Zhao Y; ''Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC.''; Int J Biol Macromol, 2020 PubMed Europe PMC Scholia
  17. Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM; ''Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers.''; Bioconjug Chem, 2015 PubMed Europe PMC Scholia
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  20. Ju X, Jiao X, Ertel A, Casimiro MC, Di Sante G, Deng S, Li Z, Di Rocco A, Zhan T, Hawkins A, Stoyanova T, Andò S, Fatatis A, Lisanti MP, Gomella LG, Languino LR, Pestell RG; ''v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1.''; Cancer Res, 2016 PubMed Europe PMC Scholia
  21. Sun H, Chen Q, Liu W, Liu Y, Ruan S, Zhu C, Ruan Y, Ying S, Lin P; ''TROP2 modulates the progression in papillary thyroid carcinoma.''; J Cancer, 2021 PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
134245view00:04, 18 July 2024EweitzOntology Term : '' added !
134244view00:03, 18 July 2024EweitzOntology Term : '' added !
134243view00:01, 18 July 2024EweitzRefine legend, standardize case
126494view20:24, 9 May 2023Khanspersconverted interactions in legend to graphical lines, added xref for Ca2+
124970view20:26, 10 January 2023KhanspersOntology Term : 'signaling pathway' added !
124847view21:13, 14 December 2022EweitzModified title
124560view00:44, 9 November 2022EweitzModified title
124536view08:11, 7 November 2022Rex D A BNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ABCC1Protein4363 (Entrez Gene)
ACVRL1Protein94 (Entrez Gene)
ADAM10 Protein102 (Entrez Gene)
ADAM17 Protein6868 (Entrez Gene)
AKT1Protein4070 (Entrez Gene)
AP1Protein4070 (Entrez Gene)
ARProtein9076 (Entrez Gene)
BAXProtein581 (Entrez Gene)
BCL2Protein596 (Entrez Gene)
CASP3Protein9076 (Entrez Gene)
CCND1Protein595 (Entrez Gene)
CCNE1Protein898 (Entrez Gene)
CD56Protein9076 (Entrez Gene)
CDH1Protein999 (Entrez Gene)
CDK2Protein1017 (Entrez Gene)
CDK4Protein1019 (Entrez Gene)
CDKN1BProtein1027 (Entrez Gene)
CDKN2AProtein1029 (Entrez Gene)
CLDN1Protein9076 (Entrez Gene)
CLDN7Protein1366 (Entrez Gene)
CREB1Protein3725 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
EGFRProtein1956 (Entrez Gene)
FN1Protein2335 (Entrez Gene)
IGF1Protein3479 (Entrez Gene)
IGF1RProtein3480 (Entrez Gene)
IGF2Protein3481 (Entrez Gene)
IGF2RProtein3482 (Entrez Gene)
ITGA5Protein3678 (Entrez Gene)
ITGB1Protein3688 (Entrez Gene)
JAK2GeneProduct3717 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
MAPK1Protein9076 (Entrez Gene)
MAPK3Protein9076 (Entrez Gene)
MAPK8Protein9076 (Entrez Gene)
MAPK9Protein9076 (Entrez Gene)
MDKProtein4192 (Entrez Gene)
MMP13Protein4322 (Entrez Gene)
MMP2Protein1111 (Entrez Gene)
MYCProtein9076 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NOTCH1Protein4851 (Entrez Gene)
NUMBRna8650 (Entrez Gene)
OCT3/4Protein9076 (Entrez Gene)
PAK4Protein10298 (Entrez Gene)
PARP1Protein9076 (Entrez Gene)
PDPK1Protein4070 (Entrez Gene)
PECAM1Protein5175 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PRKAA2Protein4851 (Entrez Gene)
PRKCAProtein5578 (Entrez Gene)
PRKCDProtein5580 (Entrez Gene)
PSAProtein9076 (Entrez Gene)
PSEN1 Protein5663 (Entrez Gene)
PSEN2Protein5664 (Entrez Gene)
PSMAProtein9076 (Entrez Gene)
PTENProtein5728 (Entrez Gene)
PTK2Protein5747 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
RACK1Protein10399 (Entrez Gene)
RB1Protein5925 (Entrez Gene)
SOX2Protein9076 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
STAT1Protein6772 (Entrez Gene)
STAT3Protein9076 (Entrez Gene)
SYPProtein9076 (Entrez Gene)
TACSTD2Protein4070 (Entrez Gene)
TLN1Protein7094 (Entrez Gene)
TP63Protein9076 (Entrez Gene)
VIMProtein7431 (Entrez Gene)

Annotated Interactions

No annotated interactions

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