A comprehensive analysis of different types of databases reveals that CDH1 mRNA and E-cadherin protein are not downregulated in most carcinoma tissues and carcinoma cell lines.
CDH1
Carcinoma
E-cadherin
Gene expression
Metastasis
Tumor progression
Tumor suppressor
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
15 May 2023
15 May 2023
Historique:
received:
14
07
2022
accepted:
03
05
2023
medline:
17
5
2023
pubmed:
16
5
2023
entrez:
15
5
2023
Statut:
epublish
Résumé
The CDH1 gene codes for the epithelial-cadherin (E-cad) protein, which is embedded in the plasma membrane of epithelial cells to form adherens junctions. E-cad is known to be essential for maintaining the integrity of epithelial tissues, and the loss of E-cad has been widely considered a hallmark of metastatic cancers enabling carcinoma cells to acquire the ability to migrate and invade nearby tissues. However, this conclusion has come under scrutiny. To assess how CDH1 and E-cad expression changes during cancer progression, we analyzed multiple large transcriptomics, proteomics, and immunohistochemistry datasets on clinical cancer samples and cancer cell lines to determine the CDH1 mRNA and E-cad protein expression profiles in tumor and normal cells. In contrast to the textbook knowledge of the loss of E-cad during tumor progression and metastasis, the levels of CDH1 mRNA and E-cad protein are either upregulated or remain unchanged in most carcinoma cells compared to normal cells. In addition, the CDH1 mRNA upregulation occurs in the early stages of tumor development and the levels remain elevated as tumors progress to later stages across most carcinoma types. Furthermore, E-cad protein levels are not downregulated in most metastatic tumor cells compared to primary tumor cells. The CDH1 mRNA and E-cad protein levels are positively correlated, and the CDH1 mRNA levels are positively correlated to cancer patient's survival. We have discussed potential mechanisms underlying the observed expression changes in CDH1 and E-cad during tumor progression. CDH1 mRNA and E-cadherin protein are not downregulated in most tumor tissues and cell lines derived from commonly occurring carcinomas. The role of E-cad in tumor progression and metastasis may have previously been oversimplified. CDH1 mRNA levels may serve as a reliable biomarker for the diagnosis of some tumors (such as colon and endometrial carcinomas) due to the marked upregulation of CDH1 mRNA in the early stages of tumor development of these carcinomas.
Sections du résumé
BACKGROUND
BACKGROUND
The CDH1 gene codes for the epithelial-cadherin (E-cad) protein, which is embedded in the plasma membrane of epithelial cells to form adherens junctions. E-cad is known to be essential for maintaining the integrity of epithelial tissues, and the loss of E-cad has been widely considered a hallmark of metastatic cancers enabling carcinoma cells to acquire the ability to migrate and invade nearby tissues. However, this conclusion has come under scrutiny.
METHODS
METHODS
To assess how CDH1 and E-cad expression changes during cancer progression, we analyzed multiple large transcriptomics, proteomics, and immunohistochemistry datasets on clinical cancer samples and cancer cell lines to determine the CDH1 mRNA and E-cad protein expression profiles in tumor and normal cells.
RESULTS
RESULTS
In contrast to the textbook knowledge of the loss of E-cad during tumor progression and metastasis, the levels of CDH1 mRNA and E-cad protein are either upregulated or remain unchanged in most carcinoma cells compared to normal cells. In addition, the CDH1 mRNA upregulation occurs in the early stages of tumor development and the levels remain elevated as tumors progress to later stages across most carcinoma types. Furthermore, E-cad protein levels are not downregulated in most metastatic tumor cells compared to primary tumor cells. The CDH1 mRNA and E-cad protein levels are positively correlated, and the CDH1 mRNA levels are positively correlated to cancer patient's survival. We have discussed potential mechanisms underlying the observed expression changes in CDH1 and E-cad during tumor progression.
CONCLUSIONS
CONCLUSIONS
CDH1 mRNA and E-cadherin protein are not downregulated in most tumor tissues and cell lines derived from commonly occurring carcinomas. The role of E-cad in tumor progression and metastasis may have previously been oversimplified. CDH1 mRNA levels may serve as a reliable biomarker for the diagnosis of some tumors (such as colon and endometrial carcinomas) due to the marked upregulation of CDH1 mRNA in the early stages of tumor development of these carcinomas.
Identifiants
pubmed: 37189027
doi: 10.1186/s12885-023-10916-0
pii: 10.1186/s12885-023-10916-0
pmc: PMC10184369
doi:
Substances chimiques
RNA, Messenger
0
Cadherins
0
Transcription Factors
0
CDH1 protein, human
0
Antigens, CD
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
441Informations de copyright
© 2023. The Author(s).
Références
Oncol Lett. 2016 Apr;11(4):2635-2643
pubmed: 27073531
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Nature. 2015 Nov 26;527(7579):525-530
pubmed: 26560028
Nat Cell Biol. 2012 Aug;14(8):777-83
pubmed: 22854810
Histol Histopathol. 1999 Oct;14(4):1183-97
pubmed: 10506935
Nat Cell Biol. 2000 Feb;2(2):76-83
pubmed: 10655586
Nature. 2013 Jul 4;499(7456):43-9
pubmed: 23792563
Nature. 2015 Nov 26;527(7579):472-6
pubmed: 26560033
Cancer Res. 1998 May 15;58(10):2063-6
pubmed: 9605742
Nature. 2019 May;569(7757):503-508
pubmed: 31068700
Database (Oxford). 2021 Apr 7;2021:
pubmed: 33826699
FEBS J. 2016 Oct;283(20):3705-3717
pubmed: 27016044
Cell. 2014 Aug 28;158(5):1110-1122
pubmed: 25171411
Bioengineering (Basel). 2021 May 11;8(5):
pubmed: 34064908
Nat Cell Biol. 2000 Feb;2(2):84-9
pubmed: 10655587
Oncogene. 2021 Mar;40(11):2081-2095
pubmed: 33627787
Front Oncol. 2017 Jul 26;7:158
pubmed: 28798901
Nature. 2012 Mar 28;483(7391):603-7
pubmed: 22460905
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
Am J Physiol Renal Physiol. 2003 Jul;285(1):F130-42
pubmed: 12644442
Cell. 2017 Feb 9;168(4):670-691
pubmed: 28187288
J Biol Chem. 2000 Jan 28;275(4):2727-32
pubmed: 10644736
Science. 1995 Jan 20;267(5196):386-9
pubmed: 7824937
Development. 1988 Apr;102(4):639-55
pubmed: 3048970
Cancer Cell Int. 2003 Oct 14;3(1):17
pubmed: 14613514
Trends Cell Biol. 2019 Mar;29(3):212-226
pubmed: 30594349
EMBO J. 2021 Sep 15;40(18):e108647
pubmed: 34459003
Biomed Microdevices. 2019 Nov 23;21(4):101
pubmed: 31760501
Cancer Res. 2008 May 15;68(10):3645-54
pubmed: 18483246
Dev Dyn. 2008 Oct;237(10):2755-68
pubmed: 18773493
J Biol Chem. 2004 Oct 8;279(41):43061-9
pubmed: 15292248
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3357-8
pubmed: 11904396
Br J Cancer. 2006 Mar 13;94(5):661-71
pubmed: 16495925
Biomaterials. 2016 Mar;81:72-83
pubmed: 26724455
Mol Cell Proteomics. 2005 Dec;4(12):1920-32
pubmed: 16127175
J Pathol. 1993 Feb;169(2):245-50
pubmed: 8383197
Biochim Biophys Acta. 2007 May;1773(5):642-52
pubmed: 16926057
Nat Rev Mol Cell Biol. 2009 Jul;10(7):445-57
pubmed: 19546857
Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560
pubmed: 31114875
Biophys J. 2005 Aug;89(2):1374-88
pubmed: 15923238
Mol Cancer. 2010 Jul 07;9:179
pubmed: 20609236
Neoplasia. 2017 Aug;19(8):649-658
pubmed: 28732212
Chin J Cancer. 2011 Feb;30(2):124-37
pubmed: 21272445
Oncogene. 2018 Aug;37(35):4769-4780
pubmed: 29780167
Sci Rep. 2015 Jun 08;5:10775
pubmed: 26053859
J Clin Med. 2016 Apr 29;5(5):
pubmed: 27136592
Mol Oncol. 2017 Jul;11(7):755-769
pubmed: 28548345
J Biol Chem. 2000 Feb 4;275(5):3328-34
pubmed: 10652321
Sci Rep. 2019 Nov 13;9(1):16668
pubmed: 31723226
Dev Cell. 2008 Jun;14(6):818-29
pubmed: 18539112
EMBO J. 1995 Dec 15;14(24):6107-15
pubmed: 8557030
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
J Biomech Eng. 2017 Feb 1;139(2):
pubmed: 27814431
Science. 2002 May 17;296(5571):1308-13
pubmed: 11964443
J Cell Biol. 2014 Mar 3;204(5):839-56
pubmed: 24590176
Cell. 2005 Dec 2;123(5):903-15
pubmed: 16325583
Am J Pathol. 1993 Dec;143(6):1731-42
pubmed: 8256859
Biochem Biophys Res Commun. 2013 May 24;435(1):58-63
pubmed: 23618854
Science. 2016 Apr 8;352(6282):167-9
pubmed: 27124449
J Pathol. 1998 Jul;185(3):262-6
pubmed: 9771479
Nature. 2019 Sep;573(7774):439-444
pubmed: 31485072
J Cell Sci. 2012 Oct 1;125(Pt 19):4417-22
pubmed: 23165231
Cancer Res. 2010 Jul 15;70(14):5706-16
pubmed: 20570886
Cell. 2005 Dec 2;123(5):889-901
pubmed: 16325582
Tissue Barriers. 2017 Jul 3;5(3):e1356900
pubmed: 28783415
Front Oncol. 2019 Oct 04;9:989
pubmed: 31637214
Am J Physiol Renal Physiol. 2003 May;284(5):F911-24
pubmed: 12505862
J Clin Oncol. 2012 Feb 10;30(5):525-32
pubmed: 22253462
Nat Commun. 2019 Dec 12;10(1):5679
pubmed: 31831737
Cell. 2020 Jan 23;180(2):387-402.e16
pubmed: 31978347
Nat Rev Mol Cell Biol. 2020 Jun;21(6):341-352
pubmed: 32300252
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E854-63
pubmed: 26831077
Cell Mol Life Sci. 2016 Sep;73(18):3535-53
pubmed: 27151512
Am J Pathol. 2019 Jan;189(1):94-103
pubmed: 30312581
Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):5931-5937
pubmed: 32127478
Pathol Int. 2016 Apr;66(4):183-92
pubmed: 26897041
Cell. 2016 Jun 30;166(1):21-45
pubmed: 27368099
J Mol Biol. 2007 Oct 19;373(2):401-11
pubmed: 17850815
Biophys J. 2005 Dec;89(6):3895-903
pubmed: 16183887
Genes Dev. 2006 Dec 1;20(23):3199-214
pubmed: 17158740
Neoplasia. 2022 Mar;25:18-27
pubmed: 35078134
Cancer Res. 2000 Aug 15;60(16):4346-8
pubmed: 10969774
Acta Naturae. 2015 Apr-Jun;7(2):17-28
pubmed: 26085941
Cell Adh Migr. 2012 Jul-Aug;6(4):365-73
pubmed: 22796940
Cancer Res. 2006 Sep 1;66(17):8319-26
pubmed: 16951136
Nat Commun. 2015 Aug 14;6:7998
pubmed: 26272476
Am J Pathol. 1993 Apr;142(4):987-93
pubmed: 7682767
PLoS One. 2009 Nov 30;4(11):e8027
pubmed: 19956566
Mol Biol Cell. 2011 Jul 15;22(14):2423-35
pubmed: 21613543
Mol Biol Cell. 2016 Nov 1;27(21):3233-3244
pubmed: 27582386