E-Cadherin in Pancreatic Ductal Adenocarcinoma: A Multifaceted Actor During EMT

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Apr 26

PMID 32331358

Citations 38

Authors

Michele Sommariva

Nicoletta Gagliano

Affiliations

Soon will be listed here.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a step-wise process observed in normal and tumor cells leading to a switch from epithelial to mesenchymal phenotype. In tumors, EMT provides cancer cells with a metastatic phenotype characterized by E-cadherin down-regulation, cytoskeleton reorganization, motile and invasive potential. E-cadherin down-regulation is known as a key event during EMT. However, E-cadherin expression can be influenced by the different experimental settings and environmental stimuli so that the paradigm of EMT based on the loss of E-cadherin determining tumor cell behavior and fate often becomes an open question. In this review, we aimed at focusing on some critical points in order to improve the knowledge of the dynamic role of epithelial cells plasticity in EMT and, specifically, address the role of E-cadherin as a marker for the EMT axis.

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References

Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez R, Wang Y . Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010; 329(5993):849-53. PMC: 3732486. DOI: 10.1126/science.1188510. View

Riedl E, Stockl J, Majdic O, Scheinecker C, Knapp W, Strobl H . Ligation of E-cadherin on in vitro-generated immature Langerhans-type dendritic cells inhibits their maturation. Blood. 2000; 96(13):4276-84. View

Wang M, Ren D, Guo W, Huang S, Wang Z, Li Q . N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells. Int J Oncol. 2015; 48(2):595-606. DOI: 10.3892/ijo.2015.3270. View

Sichien D, Lambrecht B, Guilliams M, Scott C . Development of conventional dendritic cells: from common bone marrow progenitors to multiple subsets in peripheral tissues. Mucosal Immunol. 2017; 10(4):831-844. DOI: 10.1038/mi.2017.8. View

Iacobuzio-Donahue C, Fu B, Yachida S, Luo M, Abe H, Henderson C . DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009; 27(11):1806-13. PMC: 2668706. DOI: 10.1200/JCO.2008.17.7188. View

Steinhusen U, Weiske J, Badock V, Tauber R, Bommert K, Huber O . Cleavage and shedding of E-cadherin after induction of apoptosis. J Biol Chem. 2000; 276(7):4972-80. DOI: 10.1074/jbc.M006102200. View

Chu G, Kimmelman A, Hezel A, DePinho R . Stromal biology of pancreatic cancer. J Cell Biochem. 2007; 101(4):887-907. DOI: 10.1002/jcb.21209. View

Lewis-Tuffin L, Rodriguez F, Giannini C, Scheithauer B, Necela B, Sarkaria J . Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype. PLoS One. 2010; 5(10):e13665. PMC: 2965143. DOI: 10.1371/journal.pone.0013665. View

Miyamoto H, Murakami T, Tsuchida K, Sugino H, Miyake H, Tashiro S . Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins. Pancreas. 2004; 28(1):38-44. DOI: 10.1097/00006676-200401000-00006. View

10.

Rehli M, Sulzbacher S, Pape S, Ravasi T, Wells C, Heinz S . Transcription factor Tfec contributes to the IL-4-inducible expression of a small group of genes in mouse macrophages including the granulocyte colony-stimulating factor receptor. J Immunol. 2005; 174(11):7111-22. DOI: 10.4049/jimmunol.174.11.7111. View

11.

Gil O, Lee C, Ariztia E, Wang F, Smith P, Hope J . Lysophosphatidic acid (LPA) promotes E-cadherin ectodomain shedding and OVCA429 cell invasion in an uPA-dependent manner. Gynecol Oncol. 2007; 108(2):361-9. DOI: 10.1016/j.ygyno.2007.10.027. View

12.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

13.

Shintani Y, Fukumoto Y, Chaika N, Grandgenett P, Hollingsworth M, Wheelock M . ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2007; 122(1):71-7. DOI: 10.1002/ijc.23027. View

14.

George J, Jolly M, Xu S, Somarelli J, Levine H . Survival Outcomes in Cancer Patients Predicted by a Partial EMT Gene Expression Scoring Metric. Cancer Res. 2017; 77(22):6415-6428. PMC: 5690883. DOI: 10.1158/0008-5472.CAN-16-3521. View

15.

Locati M, Curtale G, Mantovani A . Diversity, Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol. 2019; 15:123-147. PMC: 7176483. DOI: 10.1146/annurev-pathmechdis-012418-012718. View

16.

Li Y, Ji X . Relationship between expression of E-cadherin-catenin complex and clinicopathologic characteristics of pancreatic cancer. World J Gastroenterol. 2003; 9(2):368-72. PMC: 4611349. DOI: 10.3748/wjg.v9.i2.368. View

17.

French J, Cresswell J, Wong W, Seymour K, Charnley R, Kirby J . T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?. Br J Cancer. 2002; 87(9):1034-41. PMC: 2364324. DOI: 10.1038/sj.bjc.6600597. View

18.

Jakob T, Udey M . Regulation of E-cadherin-mediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo. J Immunol. 1998; 160(8):4067-73. View

19.

Mezouar S, Omar Osman I, Melenotte C, Slimani C, Chartier C, Raoult D . High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever. Front Cell Infect Microbiol. 2019; 9:219. PMC: 6598114. DOI: 10.3389/fcimb.2019.00219. View

20.

Henson S, Akbar A . KLRG1--more than a marker for T cell senescence. Age (Dordr). 2009; 31(4):285-91. PMC: 2813054. DOI: 10.1007/s11357-009-9100-9. View