TROP2 regulatory signaling (Homo sapiens)

From WikiPathways

Revision as of 00:44, 9 November 2022 by Eweitz (Talk | contribs)
Jump to: navigation, search
11TACSTD235151, 61720, 4012214In the leading edges of prostate cancer cells plated on FN EnhancesGC cell tolerance tochemotherapyProteinTROP2dimerIntracellular(TROP2-ICD) Up-regulationEnhanceddirectionalmigrationTROP2 prevents IGF1 & MDKbinding to IGF1R &ALK, respectively, bycompetitive bindingInHUVECsIn LNCaP cells and xenograftsleading toDNA condensationand decrease inhistone methylationInMTE-4-14 cellsIn GBC-SD andSGC-996 cellsInHCT116cells35, 37Ca2+CLDN1CLDN734PARP1CD56PSMAPSASOX2MYCTP63OCT3/4ARUpregulatedin VCaP cells &downregulatedin LNCaP cells& 22Rv1 cells SYPInLNCaPandPC-3cells 3434ABCC1NOTCH1In BGC-823 andHGC27 cells 2222222224CDKN2A24Cell cycleregulation2424PRKAA2PIK3R1PAKT1S473T3082626, 28, 3928Proliferation and migrationof HN6, SCC4,MG63, KM12SMMNNG/HOS, U2OS,MTE4-14 andPC-9/GR cells10, 26, 28MMP241In 8505C,K1 andFT-133 cellsAP14112, 41MAPK8MAPK9Y185T183Y185T183MAPK1T185MAPK3Y187T202Y20413, 19, 21, 40, 414141PTENS380PDPK139393939IGF18, 11MDK8, 11894, 9PRKCAPRKCD4CASP321In A549NSCLCs2121MMP13PECAM1EGFRY1173In A549NSCLCs21ACVRL1Y1604IGF1RY1136Y1151Y1135Y115088888, 19InHeLacells88RAC1GTP11ITGB11, 6ITGA5TLN1TLN1119, 40CREB1S133STAT1Y701RB1S780NFKB1SRC12PTK2Y416Y397InPC3-2cellsJUNIn FT-133,FADU andMTE-4-14 cells25ADAM10 TACSTD2S322CDH117Affinity:CLDN7>CLDN15, 18BCL2BAXInA2780,Hela and C33Acells7, 13CTNNB1FN1VIMCDH1Induces EMTin MGC803cells5, 13CDK4InHelaandC33Acells13In LNCaP &TRAMP C2 cells36CCND1CCNE1CDK2CDKN1BInPanc02, Hela and C33AcellsJAK2Y1008STAT3Y1007S727Y7051414In LN-229and U87-MGcells14PSEN2ADAM17 15TACSTD215TROP2-ICD15PSEN1 ADAM17 153, 1515In LNCaPcells 15365Upregulatedin Panc02, Hela,C33ATRAMP C2 &HEP2 cells anddown-regulatedin MTE-4-14 cells53434343434InLNCaP,PC-3,VCaP,DU-145cells34In LNCaP cells and xenografts,PC-3, andVCaP cells34343434CTNNB171111In TROP2-overexpressingH1299,CL1-0and H23 lungcancer cells11In TROP2-overexpressingH1299,CL1-0and H23 lungcancer cells1111InH1299 andH23 cellsIGF2R10IGF21010RACK110121212391219, 403419CYNUCYNUFACEIn MTE-4-14 cells191919, 4021mRNAProteinmRNAProteinmRNA 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 Nucleus Figure Legend TROP2 Regulatory signaling networkPAK4S4741115NUMBIn v-SRC PECcells 1539


Description

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

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Zhao W, Jia L, Kuai X, Tang Q, Huang X, Yang T, Qiu Z, Zhu J, Huang J, Huang W, Feng Z; ''The role and molecular mechanism of Trop2 induced epithelial-mesenchymal transition through mediated β-catenin in gastric cancer.''; Cancer Med, 2019 PubMed Europe PMC Scholia
  2. Wang XD, Wang Q, Chen XL, Huang JF, Yin Y, Da P, Wu H; ''Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway.''; Mol Med Rep, 2015 PubMed Europe PMC Scholia
  3. Trerotola M, Ganguly KK, Fazli L, Fedele C, Lu H, Dutta A, Liu Q, De Angelis T, Riddell LW, Riobo NA, Gleave ME, Zoubeidi A, Pestell RG, Altieri DC, Languino LR; ''Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts.''; Oncotarget, 2015 PubMed Europe PMC Scholia
  4. Gu QZ, Nijiati A, Gao X, Tao KL, Li CD, Fan XP, Tian Z; ''TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling.''; Mol Med Rep, 2018 PubMed Europe PMC Scholia
  5. Guan H, Guo Z, Liang W, Li H, Wei G, Xu L, Xiao H, Li Y; ''Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways.''; BMC Cancer, 2017 PubMed Europe PMC Scholia
  6. Hou J, Lv A, Deng Q, Zhang G, Hu X, Cui H; ''TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway.''; Oncol Rep, 2019 PubMed Europe PMC Scholia
  7. Tang G, Tang Q, Jia L, Chen Y, Lin L, Kuai X, Gong A, Feng Z; ''TROP2 increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/Akt signaling pathway.''; Int J Mol Med, 2019 PubMed Europe PMC Scholia
  8. Trerotola M, Jernigan DL, Liu Q, Siddiqui J, Fatatis A, Languino LR; ''Trop-2 promotes prostate cancer metastasis by modulating β(1) integrin functions.''; Cancer Res, 2013 PubMed Europe PMC Scholia
  9. Li X, Teng S, Zhang Y, Zhang W, Zhang X, Xu K, Yao H, Yao J, Wang H, Liang X, Hu Z; ''TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT.''; Oncotarget, 2017 PubMed Europe PMC Scholia
  10. Gao XY, Zhu YH, Zhang LX, Lu HY, Jiang AG; ''siRNA targeting of Trop2 suppresses the proliferation and invasion of lung adenocarcinoma H460 cells.''; Exp Ther Med, 2015 PubMed Europe PMC Scholia
  11. Yang J, Zhu Z, Wang H, Li F, Du X, Ma RZ; ''Trop2 regulates the proliferation and differentiation of murine compact-bone derived MSCs.''; Int J Oncol, 2013 PubMed Europe PMC Scholia
  12. Hsu EC, Rice MA, Bermudez A, Marques FJG, Aslan M, Liu S, Ghoochani A, Zhang CA, Chen YS, Zlitni A, Kumar S, Nolley R, Habte F, Shen M, Koul K, Peehl DM, Zoubeidi A, Gambhir SS, Kunder CA, Pitteri SJ, Brooks JD, Stoyanova T; ''Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1.''; Proc Natl Acad Sci U S A, 2020 PubMed Europe PMC Scholia
  13. Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM; ''Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys.''; Clin Cancer Res, 2011 PubMed Europe PMC Scholia
  14. Guerra E, Trerotola M, Aloisi AL, Tripaldi R, Vacca G, La Sorda R, Lattanzio R, Piantelli M, Alberti S; ''The Trop-2 signalling network in cancer growth.''; Oncogene, 2013 PubMed Europe PMC Scholia
  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
  18. Zimmers SM, Browne EP, Williams KE, Jawale RM, Otis CN, Schneider SS, Arcaro KF; ''TROP2 methylation and expression in tamoxifen-resistant breast cancer.''; Cancer Cell Int, 2018 PubMed Europe PMC Scholia
  19. Lin JC, Wu YY, Wu JY, Lin TC, Wu CT, Chang YL, Jou YS, Hong TM, Yang PC; ''TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung adenocarcinoma.''; EMBO Mol Med, 2012 PubMed Europe PMC Scholia
  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
  22. Cubas R, Zhang S, Li M, Chen C, Yao Q; ''Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway.''; Mol Cancer, 2010 PubMed Europe PMC Scholia
  23. Stoyanova T, Goldstein AS, Cai H, Drake JM, Huang J, Witte ON; ''Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling.''; Genes Dev, 2012 PubMed Europe PMC Scholia
  24. Pavši� M; ''Trop2 Forms a Stable Dimer with Significant Structural Differences within the Membrane-Distal Region as Compared to EpCAM.''; Int J Mol Sci, 2021 PubMed Europe PMC Scholia
  25. Sun X, Jia L, Wang T, Zhang Y, Zhao W, Wang X, Chen H; ''Trop2 binding IGF2R induces gefitinib resistance in NSCLC by remodeling the tumor microenvironment.''; J Cancer, 2021 PubMed Europe PMC Scholia
  26. Mori Y, Akita K, Ojima K, Iwamoto S, Yamashita T, Morii E, Nakada H; ''Trophoblast cell surface antigen 2 (Trop-2) phosphorylation by protein kinase C α/δ (PKCα/δ) enhances cell motility.''; J Biol Chem, 2019 PubMed Europe PMC Scholia
  27. Guerra E, Trerotola M, Tripaldi R, Aloisi AL, Simeone P, Sacchetti A, Relli V, D'Amore A, La Sorda R, Lattanzio R, Piantelli M, Alberti S; ''Trop-2 Induces Tumor Growth Through AKT and Determines Sensitivity to AKT Inhibitors.''; Clin Cancer Res, 2016 PubMed Europe PMC Scholia
  28. Liu X, Li S, Yi F; ''Trop2 gene: a novel target for cervical cancer treatment.''; J Cancer Res Clin Oncol, 2014 PubMed Europe PMC Scholia
  29. Trerotola M, Guerra E, Ali Z, Aloisi AL, Ceci M, Simeone P, Acciarito A, Zanna P, Vacca G, D'Amore A, Boujnah K, Garbo V, Moschella A, Lattanzio R, Alberti S; ''Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis.''; Neoplasia, 2021 PubMed Europe PMC Scholia
  30. Liu T, Liu Y, Bao X, Tian J, Yang X; ''Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway.''; PLoS One, 2013 PubMed Europe PMC Scholia
  31. Kamble PR, Rane S, Breed AA, Joseph S, Mahale SD, Pathak BR; ''Proteolytic cleavage of Trop2 at Arg87 is mediated by matriptase and regulated by Val194.''; FEBS Lett, 2020 PubMed Europe PMC Scholia
  32. Sawanyawisuth K, Tantapotinan N, Wongkham C, Riggins GJ, Kraiklang R, Wongkham S, Puapairoj A; ''Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma.''; Ann Hepatol, 2016 PubMed Europe PMC Scholia
  33. Trerotola M, Li J, Alberti S, Languino LR; ''Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis.''; J Cell Physiol, 2012 PubMed Europe PMC Scholia
  34. Sun X, Xing G, Zhang C, Lu K, Wang Y, He X; ''Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β-catenin pathway.''; Cell Biochem Funct, 2020 PubMed Europe PMC Scholia
  35. Wu B, Yu C, Zhou B, Huang T, Gao L, Liu T, Yang X; ''Overexpression of TROP2 promotes proliferation and invasion of ovarian cancer cells.''; Exp Ther Med, 2017 PubMed Europe PMC Scholia
  36. Zhao W, Kuai X, Zhou X, Jia L, Wang J, Yang X, Tian Z, Wang X, Lv Q, Wang B, Zhao Y, Huang W; ''Trop2 is a potential biomarker for the promotion of EMT in human breast cancer.''; Oncol Rep, 2018 PubMed Europe PMC Scholia
  37. Guo X, Zhu X, Zhao L, Li X, Cheng D, Feng K; ''Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway.''; Tumour Biol, 2017 PubMed Europe PMC Scholia
  38. Guerra E, Trerotola M, Relli V, Lattanzio R, Tripaldi R, Vacca G, Ceci M, Boujnah K, Garbo V, Moschella A, Zappacosta R, Simeone P, de Lange R, Weidle UH, Rotelli MT, Picciariello A, Depalo R, Querzoli P, Pedriali M, Bianchini E, Angelucci D, Pizzicannella G, Di Loreto C, Piantelli M, Antolini L, Sun XF, Altomare DF, Alberti S; ''Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.''; Neoplasia, 2021 PubMed Europe PMC Scholia
  39. Kuai X, Jia L, Yang T, Huang X, Zhao W, Zhang M, Chen Y, Zhu J, Feng Z, Tang Q; ''Trop2 Promotes Multidrug Resistance by Regulating Notch1 Signaling Pathway in Gastric Cancer Cells.''; Med Sci Monit, 2020 PubMed Europe PMC Scholia
  40. McDougall AR, Hooper SB, Zahra VA, Cole TJ, Lo CY, Doran T, Wallace MJ; ''Trop2 regulates motility and lamellipodia formation in cultured fetal lung fibroblasts.''; Am J Physiol Lung Cell Mol Physiol, 2013 PubMed Europe PMC Scholia
  41. Sin STK, Li Y, Liu M, Ma S, Guan XY; ''TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling.''; Gynecol Oncol, 2019 PubMed Europe PMC Scholia

History

View all...
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

View all...
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+Metabolite
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

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5300"
Personal tools