TROP2 regulatory signaling (WP5300)

Homo sapiens

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


Rex D A B , Eric Weitz , and Kristina Hanspers


last edited

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Homo sapiens



Pathway Ontology

signaling pathway


Label Type Compact URI Comment
Ca2+ Metabolite chebi:29108
JAK2 GeneProduct ncbigene:3717
TACSTD2 Protein ncbigene:4070
CLDN1 Protein ncbigene:9076
CLDN7 Protein ncbigene:1366
PARP1 Protein ncbigene:9076
CD56 Protein ncbigene:9076
PSMA Protein ncbigene:9076
PSA Protein ncbigene:9076
SOX2 Protein ncbigene:9076
MYC Protein ncbigene:9076
TP63 Protein ncbigene:9076
OCT3/4 Protein ncbigene:9076
AR Protein ncbigene:9076
SYP Protein ncbigene:9076
ABCC1 Protein ncbigene:4363
NOTCH1 Protein ncbigene:4851
CDKN2A Protein ncbigene:1029
PRKAA2 Protein ncbigene:4851
PIK3R1 Protein ncbigene:5295
AKT1 Protein ncbigene:4070
MMP2 Protein ncbigene:1111
AP1 Protein ncbigene:4070
MAPK8 Protein ncbigene:9076
MAPK9 Protein ncbigene:9076
MAPK1 Protein ncbigene:9076
MAPK3 Protein ncbigene:9076
PTEN Protein ncbigene:5728
PDPK1 Protein ncbigene:4070
IGF1 Protein ncbigene:3479
MDK Protein ncbigene:4192
PRKCA Protein ncbigene:5578
PRKCD Protein ncbigene:5580
CASP3 Protein ncbigene:9076
MMP13 Protein ncbigene:4322
PECAM1 Protein ncbigene:5175
EGFR Protein ncbigene:1956
ACVRL1 Protein ncbigene:94
IGF1R Protein ncbigene:3480
RAC1 Protein ncbigene:5879
ITGB1 Protein ncbigene:3688
ITGA5 Protein ncbigene:3678
TLN1 Protein ncbigene:7094
TLN1 Protein ncbigene:7094
CREB1 Protein ncbigene:3725
STAT1 Protein ncbigene:6772
RB1 Protein ncbigene:5925
NFKB1 Protein ncbigene:4790
SRC Protein ncbigene:6714
PTK2 Protein ncbigene:5747
JUN Protein ncbigene:3725
ADAM10 Protein ncbigene:102
TACSTD2 Protein ncbigene:4070
CDH1 Protein ncbigene:999
BCL2 Protein ncbigene:596
BAX Protein ncbigene:581
CTNNB1 Protein ncbigene:1499
FN1 Protein ncbigene:2335
VIM Protein ncbigene:7431
CDH1 Protein ncbigene:999
CDK4 Protein ncbigene:1019
CCND1 Protein ncbigene:595
CCNE1 Protein ncbigene:898
CDK2 Protein ncbigene:1017
CDKN1B Protein ncbigene:1027
STAT3 Protein ncbigene:9076
PSEN2 Protein ncbigene:5664
ADAM17 Protein ncbigene:6868
TACSTD2 Protein ncbigene:4070
PSEN1 Protein ncbigene:5663
ADAM17 Protein ncbigene:6868
CTNNB1 Protein ncbigene:1499
IGF2R Protein ncbigene:3482
IGF2 Protein ncbigene:3481
RACK1 Protein ncbigene:10399
PAK4 Protein ncbigene:10298


  1. 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. Nakatsukasa M, Kawasaki S, Yamasaki K, Fukuoka H, Matsuda A, Tsujikawa M, et al. Am J Pathol. 2010 Sep;177(3):1344–55. PubMed Europe PMC Scholia
  2. Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Cubas R, Zhang S, Li M, Chen C, Yao Q. Mol Cancer. 2010 Sep 21;9:253. PubMed Europe PMC Scholia
  3. Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis. Trerotola M, Li J, Alberti S, Languino LR. J Cell Physiol. 2012 Nov;227(11):3670–7. PubMed Europe PMC Scholia
  4. TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung adenocarcinoma. Lin JC, Wu YY, Wu JY, Lin TC, Wu CT, Chang YL, et al. EMBO Mol Med. 2012 Jun;4(6):472–85. PubMed Europe PMC Scholia
  5. The Trop-2 signalling network in cancer growth. Guerra E, Trerotola M, Aloisi AL, Tripaldi R, Vacca G, La Sorda R, et al. Oncogene. 2013 Mar 21;32(12):1594–600. PubMed Europe PMC Scholia
  6. Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling. Stoyanova T, Goldstein AS, Cai H, Drake JM, Huang J, Witte ON. Genes Dev. 2012 Oct 15;26(20):2271–85. PubMed Europe PMC Scholia
  7. Trop-2 promotes prostate cancer metastasis by modulating β(1) integrin functions. Trerotola M, Jernigan DL, Liu Q, Siddiqui J, Fatatis A, Languino LR. Cancer Res. 2013 May 15;73(10):3155–67. PubMed Europe PMC Scholia
  8. Trop2 regulates the proliferation and differentiation of murine compact-bone derived MSCs. Yang J, Zhu Z, Wang H, Li F, Du X, Ma RZ. Int J Oncol. 2013 Sep;43(3):859–67. PubMed Europe PMC Scholia
  9. 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. Liu T, Liu Y, Bao X, Tian J, Liu Y, Yang X. PLoS One. 2013 Sep 27;8(9):e75864. PubMed Europe PMC Scholia
  10. Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Wang XD, Wang Q, Chen XL, Huang JF, Yin Y, Da P, et al. Mol Med Rep. 2015 Jul;12(1):865–70. PubMed Europe PMC Scholia
  11. Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts. Trerotola M, Ganguly KK, Fazli L, Fedele C, Lu H, Dutta A, et al. Oncotarget. 2015 Jun 10;6(16):14318–28. PubMed Europe PMC Scholia
  12. Trop-2 Induces Tumor Growth Through AKT and Determines Sensitivity to AKT Inhibitors. Guerra E, Trerotola M, Tripaldi R, Aloisi AL, Simeone P, Sacchetti A, et al. Clin Cancer Res. 2016 Aug 15;22(16):4197–205. PubMed Europe PMC Scholia
  13. v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1. Ju X, Jiao X, Ertel A, Casimiro MC, Di Sante G, Deng S, et al. Cancer Res. 2016 Nov 15;76(22):6723–34. PubMed Europe PMC Scholia
  14. Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway. Guo X, Zhu X, Zhao L, Li X, Cheng D, Feng K. Tumour Biol. 2017 Mar;39(3):1010428317694324. PubMed Europe PMC Scholia
  15. TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. Li X, Teng S, Zhang Y, Zhang W, Zhang X, Xu K, et al. Oncotarget. 2017 Jul 18;8(29):47052–63. PubMed Europe PMC Scholia
  16. Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways. Guan H, Guo Z, Liang W, Li H, Wei G, Xu L, et al. BMC Cancer. 2017 Jul 14;17(1):486. PubMed Europe PMC Scholia
  17. Overexpression of TROP2 promotes proliferation and invasion of ovarian cancer cells. Wu B, Yu C, Zhou B, Huang T, Gao L, Liu T, et al. Exp Ther Med. 2017 Sep;14(3):1947–52. PubMed Europe PMC Scholia
  18. TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling. Gu QZ, Nijiati A, Gao X, Tao KL, Li CD, Fan XP, et al. Mol Med Rep. 2018 Aug;18(2):1782–8. PubMed Europe PMC Scholia
  19. TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling. Sin STK, Li Y, Liu M, Ma S, Guan XY. Gynecol Oncol. 2019 Jan;152(1):185–93. PubMed Europe PMC Scholia
  20. TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway. Hou J, Lv A, Deng Q, Zhang G, Hu X, Cui H. Oncol Rep. 2019 Feb;41(2):753–64. PubMed Europe PMC Scholia
  21. The role and molecular mechanism of Trop2 induced epithelial-mesenchymal transition through mediated β-catenin in gastric cancer. Zhao W, Jia L, Kuai X, Tang Q, Huang X, Yang T, et al. Cancer Med. 2019 Mar;8(3):1135–47. PubMed Europe PMC Scholia
  22. Trophoblast cell surface antigen 2 (Trop-2) phosphorylation by protein kinase C α/δ (PKCα/δ) enhances cell motility. Mori Y, Akita K, Ojima K, Iwamoto S, Yamashita T, Morii E, et al. J Biol Chem. 2019 Jul 26;294(30):11513–24. PubMed Europe PMC Scholia
  23. TROP2 increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/Akt signaling pathway. Tang G, Tang Q, Jia L, Chen Y, Lin L, Kuai X, et al. Int J Mol Med. 2019 Dec;44(6):2161–70. PubMed Europe PMC Scholia
  24. Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1. Hsu EC, Rice MA, Bermudez A, Marques FJG, Aslan M, Liu S, et al. Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2032–42. PubMed Europe PMC Scholia
  25. Trop2 Promotes Multidrug Resistance by Regulating Notch1 Signaling Pathway in Gastric Cancer Cells. Kuai X, Jia L, Yang T, Huang X, Zhao W, Zhang M, et al. Med Sci Monit. 2020 Jan 22;26:e919566. PubMed Europe PMC Scholia
  26. Proteolytic cleavage of Trop2 at Arg87 is mediated by matriptase and regulated by Val194. Kamble PR, Rane S, Breed AA, Joseph S, Mahale SD, Pathak BR. FEBS Lett. 2020 Oct;594(19):3156–69. PubMed Europe PMC Scholia
  27. Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC. Jia L, Wang T, Ding G, Kuai X, Wang X, Wang B, et al. Int J Biol Macromol. 2020 Dec 1;164:2409–17. PubMed Europe PMC Scholia
  28. Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis. Trerotola M, Guerra E, Ali Z, Aloisi AL, Ceci M, Simeone P, et al. Neoplasia. 2021 Apr;23(4):415–28. PubMed Europe PMC Scholia
  29. Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer. Guerra E, Trerotola M, Relli V, Lattanzio R, Tripaldi R, Vacca G, et al. Neoplasia. 2021 Sep;23(9):898–911. PubMed Europe PMC Scholia
  30. Trop2 binding IGF2R induces gefitinib resistance in NSCLC by remodeling the tumor microenvironment. Sun X, Jia L, Wang T, Zhang Y, Zhao W, Wang X, et al. J Cancer. 2021 Jul 3;12(17):5310–9. PubMed Europe PMC Scholia
  31. Trop2 Forms a Stable Dimer with Significant Structural Differences within the Membrane-Distal Region as Compared to EpCAM. Pavšič M. Int J Mol Sci. 2021 Sep 30;22(19):10640. PubMed Europe PMC Scholia