Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 2: 247 - 252

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.02.018

Review

Research progress in the function of desmoglein-2 in digestive system tumors

  • Yanqing LI ,
  • Xiaoxia WANG ,
  • Xiangdong JIA ,
  • Meng REN ,
  • Tianxiang XU
Expand
  • 1.Graduate School of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014000, China
    2.Intensive Care Unit, Inner Mongolia People's Hospital, Hohhot 010017, China
    3.Abdominal Tumor Surgery, Center of Tumor, Inner Mongolia People's Hospital, Hohhot 010017, China
XU Tianxiang, E-mail:122784509@qq.com.

Received date: 2021-09-25

  Online published: 2022-03-17

Supported by

Natural Science Foundation of Inner Mongolia Autonomous Region(2019MS08085);Start Up Fund for Doctoral Research of People's Hospital of Inner Mongolia Autonomous Region(2020BS06);Health Science and Technology Planning Project(202201012)

Fold

Abstract

Desmoglein-2 (DSG2) is a member of the cadherin family. As an important part of desmoglein, DSG2 mainly plays a role in maintaining intercellular adhesion. Studies have found that DSG2 can also regulate cell proliferation, differentiation and apoptosis through signal transduction, and plays a key role in regulating intestinal epithelial barrier. With the deepening of research, more and more evidence shows that DSG2 is abnormally expressed in a variety of digestive system tumors, and the expression levels are different. The expression level is closely related to the prognosis of tumors. It is speculated that DSG2 plays different roles in the occurrence and development of different digestive system tumors. This article reviews the biological function of DSG2 and its role in digestive system tumors.

Key words： desmoglein-2 (DSG2); digestive system tumors; biological function

Cite this article

Yanqing LI , Xiaoxia WANG , Xiangdong JIA , Meng REN , Tianxiang XU . Research progress in the function of desmoglein-2 in digestive system tumors[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(2) : 247 -252 . DOI: 10.3969/j.issn.1674-8115.2022.02.018

References

1 NISHIOKA N, YASHIRO M, INOUE T, et al. A candidate tumor suppressor locus for scirrhous gastric cancer at chromosome 18q 12.2[J]. Int J Oncol, 2001, 18(2): 317-322.
2 ZOU Y, ZHANG Q, ZHANG J, et al. A common indel polymorphism of the desmoglein-2 (DSG2) is associated with sudden cardiac death in Chinese populations[J]. Forensic Sci Int, 2019, 301: 382-387.
3 FU B M. Tumor metastasis in the microcirculation[J]. Adv Exp Med Biol, 2018, 1097: 201-218.
4 KIM J, BEIDLER P, WANG H J, et al. Desmoglein-2 as a prognostic and biomarker in ovarian cancer[J]. Cancer Biol Ther, 2020, 21(12): 1154-1162.
5 JIN R, WANG X, ZANG R, et al. Desmoglein-2 modulates tumor progression and osimertinib drug resistance through the EGFR/Src/PAK1 pathway in lung adenocarcinoma[J]. Cancer Lett, 2020, 483: 46-58.
6 SUN R, MA C, WANG W, et al. Upregulation of desmoglein 2 and its clinical value in lung adenocarcinoma: a comprehensive analysis by multiple bioinformatics methods[J]. PeerJ, 2020, 8: e8420.
7 CAI F, ZHU Q, MIAO Y, et al. Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2[J]. J Cancer Res Clin Oncol, 2017, 143(1): 59-69.
8 ZHOU B X, LI Y. Significance of desmoglein-2 on cell malignant behaviors via mediating MAPK signaling in cervical cancer[J]. Kaohsiung J Med Sci, 2020, 36(5): 336-343.
9 ANGULO-URARTE A, VAN DER WAL T, HUVENEERS S. Cell-cell junctions as sensors and transducers of mechanical forces[J]. Biochim Biophys Acta Biomembr, 2020, 1862(9): 183316.
10 CELENTANO A, CIRILLO N. Desmosomes in disease: a guide for clinicians[J]. Oral Dis, 2017, 23(2): 157-167.
11 SIKORA M, ERMEL U H, SEYBOLD A, et al. Desmosome architecture derived from molecular dynamics simulations and cryo-electron tomography[J]. PNAS, 2020, 117(44): 27132-27140.
12 HOLTH?FER B, WINDOFFER R, TROYANOVSKY S, et al. Structure and function of desmosomes[J]. Int Rev Cytol, 2007, 264: 65-163.
13 BEGGS R R, DEAN W F, MATTHEYSES A L. dSTORM imaging and analysis of desmosome architecture[J]. Methods Mol Biol, 2021, 2367: 305-315.
14 UNGEWI? H, R?TZER V, MEIR M, et al. Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion[J]. Cell Mol Life Sci, 2018, 75(22): 4251-4268.
15 BELLI S, ESPOSITO D, SERVETTO A, et al. c-Src and EGFR inhibition in molecular cancer therapy: what else can we improve?[J]. Cancers (Basel), 2020,12(6):1489.
16 BISCARDI J S, MAA M C, TICE D A, et al. C-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function[J]. J Biol Chem, 1999, 274(12): 8335-8343.
17 JUNG O, CHOI Y J, KWAK T K, et al. The COOH-terminus of TM4SF5 in hepatoma cell lines regulates c-Src to form invasive protrusions via EGFR Tyr845 phosphorylation[J]. Biochim Biophys Acta, 2013, 1833(3): 629-642.
18 CVRLJEVIC A N, AKHAVAN D, WU M, et al. Activation of Src induces mitochondrial localisation of de2-7EGFR (EGFRvIII) in glioma cells: implications for glucose metabolism[J]. J Cell Sci, 2011, 124(pt 17): 2938-2950.
19 OVERMILLER A M, MCGUINN K P, ROBERTS B J, et al. C-src/Cav1-dependent activation of the EGFR by Dsg2[J]. Oncotarget, 2016, 7(25): 37536-37555.
20 SCHLEGEL N, MEIR M, HEUPEL W M, et al. Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 298(5): G774-G783.
21 UNGEWI? H, VIELMUTH F, SUZUKI S T, et al. Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase[J]. Sci Rep, 2017, 7(1): 6329.
22 LANZA A, CIRILLO N. Caspase-dependent cleavage of desmoglein 1 depends on the apoptotic stimulus[J]. Br J Dermatol, 2007,156(2):400-402.
23 CIRILLO N, LANZA M, DE ROSA A, et al. The most widespread desmosomal cadherin, desmoglein 2, is a novel target of caspase 3-mediated apoptotic machinery[J]. J Cell Biochem, 2008, 103(2): 598-606.
24 NAVA P, LAUKOETTER M G, HOPKINS A M, et al. Desmoglein-2: a novel regulator of apoptosis in the intestinal epithelium[J]. Mol Biol Cell, 2007, 18(11): 4565-4578.
25 VANBERVLIET-DEFRANCE B, DELAUNAY T, DAUNIZEAU T, et al. Cisplatin unleashes Toll-like receptor 3-mediated apoptosis through the downregulation of c-FLIP in malignant mesothelioma[J]. Cancer Lett, 2020, 472: 29-39.
26 BEDOUI S, HEROLD M J, STRASSER A. Emerging connectivity of programmed cell death pathways and its physiological implications[J]. Nat Rev Mol Cell Biol, 2020, 21(11): 678-695.
27 ADESHAKIN F O, ADESHAKIN A O, AFOLABI L O, et al. Mechanisms for modulating anoikis resistance in cancer and the relevance of metabolic reprogramming[J]. Front Oncol, 2021, 11: 626577.
28 董敏, 史恩溢, 顾丽, 等. 修订版Lauren分型对胃癌患者临床病理学特征及预后的影响[J]. 临床与实验病理学杂志, 2021, 37(4): 398-401.
29 ZHANG H Y, CHANG H, FAN X N, et al. Expression of adhesion molecules and mucins in human and rhesus macaque gastrointestinal epithelial cells[J]. Histol Histopathol, 2011, 26(11): 1405-1413.
30 YASHIRO M, NISHIOKA N, HIRAKAWA K. Decreased expression of the adhesion molecule desmoglein-2 is associated with diffuse-type gastric carcinoma[J]. Eur J Cancer, 2006, 42(14): 2397-2403.
31 CAO Y, CHANG H, LI L, et al. Alteration of adhesion molecule expression and cellular polarity in hepatocellular carcinoma[J]. Histopathology, 2007, 51(4): 528-538.
32 HAN C P, YU Y H, WANG A G, et al. Desmoglein-2 overexpression predicts poor prognosis in hepatocellular carcinoma patients[J]. Eur Rev Med Pharmacol Sci, 2018, 22(17): 5481-5489.
33 LEE S H, KIM J M, LEE D G, et al. Loss of desmoglein-2 promotes gallbladder carcinoma progression and resistance to EGFR-targeted therapy through Src kinase activation[J]. Cell Death Differ, 2021, 28(3): 968-984.
34 AHN J Y, LEE J S, MIN H Y, et al. Acquired resistance to 5-fluorouracil via HSP90/Src-mediated increase in thymidylate synthase expression in colon cancer[J]. Oncotarget, 2015, 6(32): 32622-32633.
35 TAN Q, WANG H, HU Y, et al. Src/STAT3-dependent heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to doxorubicin by promoting autophagy[J]. Cancer Sci, 2015, 106(8): 1023-1032.
36 ZHANG K, WANG X, WANG H. Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line[J]. Mol Med Rep, 2014, 10(4): 2065-2072.
37 HüTZ K, ZEILER J, SACHS L, et al. Loss of desmoglein 2 promotes tumorigenic behavior in pancreatic cancer cells[J]. Mol Carcinog, 2017, 56(8): 1884-1895.
38 FERRO R, FALASCA M. Emerging role of the KRAS-PDK1 axis in pancreatic cancer[J]. World J Gastroenterol, 2014, 20(31): 10752-10757.
39 ZHURINSKY J, SHTUTMAN M, BEN-ZE'EV A. Plakoglobin and beta-catenin: protein interactions, regulation and biological roles[J]. J Cell Sci, 2000, 113 ( Pt 18): 3127-3139.
40 AKTARY Z, PASDAR M. Plakoglobin: role in tumorigenesis and metastasis[J]. Int J Cell Biol, 2012, 2012: 189521.
41 SALOMON D, SACCO P A, ROY S G, et al. Regulation of beta-catenin levels and localization by overexpression of plakoglobin and inhibition of the ubiquitin-proteasome system[J]. J Cell Biol, 1997, 139(5): 1325-1335.
42 GROSS A, PACK L A P, SCHACHT G M, et al. Desmoglein 2, but not desmocollin 2, protects intestinal epithelia from injury[J]. Mucosal Immunol, 2018, 11(6): 1630-1639.
43 SCHLEGEL N, BOERNER K, WASCHKE J. Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases: lessons from experimental models and patients[J]. Acta Physiol (Oxf), 2021, 231(1): e13492.
44 SPINDLER V, MEIR M, VIGH B, et al. Loss of desmoglein 2 contributes to the pathogenesis of Crohn's disease[J]. Inflamm Bowel Dis, 2015, 21(10): 2349-2359.
45 KAMEKURA R, KOLEGRAFF K N, NAVA P, et al. Loss of the desmosomal cadherin desmoglein-2 suppresses colon cancer cell proliferation through EGFR signaling[J]. Oncogene, 2014, 33(36): 4531-4536.
46 YANG T, GU X, JIA L, et al. DSG2 expression is low in colon cancer and correlates with poor survival[J]. BMC Gastroenterol, 2021, 21(1): 7.
Options
Outlines

/

〈 〉