Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma.
Adenocarcinoma
/ genetics
Adenocarcinoma of Lung
/ genetics
Cell Adhesion Molecules
/ metabolism
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Junctional Adhesion Molecules
/ genetics
Lung Neoplasms
/ pathology
Wnt Signaling Pathway
beta Catenin
/ metabolism
Invasion
Junctional adhesion molecule-like protein
Lung adenocarcinoma
Migration
Tumor progression
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
07 06 2022
07 06 2022
Historique:
received:
27
03
2022
accepted:
24
05
2022
entrez:
7
6
2022
pubmed:
8
6
2022
medline:
10
6
2022
Statut:
epublish
Résumé
Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD. qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms. JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.
Sections du résumé
BACKGROUND
Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD.
METHODS
qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms.
RESULTS
JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G
CONCLUSIONS
Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.
Identifiants
pubmed: 35672776
doi: 10.1186/s12967-022-03457-w
pii: 10.1186/s12967-022-03457-w
pmc: PMC9171988
doi:
Substances chimiques
Cell Adhesion Molecules
0
JAML protein, human
0
Junctional Adhesion Molecules
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
260Informations de copyright
© 2022. The Author(s).
Références
Cancer Res. 2020 Nov 15;80(22):4878-4885
pubmed: 32816855
Med Sci Monit. 2022 Jan 16;28:e933503
pubmed: 35034089
J Cell Biol. 2008 Dec 15;183(6):1159-73
pubmed: 19064666
Nat Commun. 2015 Dec 04;6:8971
pubmed: 26634437
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29
pubmed: 25559415
Cell. 2011 Oct 14;147(2):275-92
pubmed: 22000009
Nat Commun. 2019 Mar 29;10(1):1405
pubmed: 30926812
CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32
pubmed: 26808342
Front Oncol. 2021 Mar 11;11:565676
pubmed: 33777731
Int J Cancer. 2009 Sep 15;125(6):1343-51
pubmed: 19533747
Nat Rev Cancer. 2003 Jan;3(1):46-54
pubmed: 12509766
Nat Cell Biol. 2014 Jun;16(6):488-94
pubmed: 24875735
Mucosal Immunol. 2014 Sep;7(5):1221-32
pubmed: 24621992
Cancer Immunol Res. 2018 Jan;6(1):87-97
pubmed: 29141981
Carcinogenesis. 2015 Jan;36(1):41-8
pubmed: 25416560
J Clin Invest. 2009 Jun;119(6):1420-8
pubmed: 19487818
Ann Surg Oncol. 2012 Dec;19(13):4330-6
pubmed: 22549289
Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):75-83
pubmed: 18948633
Oncogene. 2017 Mar 30;36(13):1779-1792
pubmed: 27641329
Cancer Cell Int. 2022 Mar 5;22(1):111
pubmed: 35248033
Biochem Biophys Res Commun. 2009 Mar 6;380(2):387-91
pubmed: 19250634
Cancer Res. 2008 Apr 1;68(7):2194-203
pubmed: 18381425
J Cell Physiol. 2007 Nov;213(2):374-83
pubmed: 17680632
Mol Biol Cell. 2005 Jun;16(6):2694-703
pubmed: 15800062
Cancer Sci. 2017 Nov;108(11):2306-2314
pubmed: 28837251
Clin Sci (Lond). 2019 Jun 3;133(11):1215-1228
pubmed: 31101724
Sci Transl Med. 2015 Mar 18;7(279):279ra40
pubmed: 25787766
J Cell Biochem. 2019 Oct;120(10):18117-18127
pubmed: 31161679
Mol Cancer. 2017 Jul 17;16(1):124
pubmed: 28716029
Cell. 2016 Jun 30;166(1):21-45
pubmed: 27368099
Nat Rev Drug Discov. 2012 Feb 01;11(2):109-24
pubmed: 22293567
Curr Opin Genet Dev. 1998 Feb;8(1):95-102
pubmed: 9529612
Blood. 2003 Nov 1;102(9):3371-8
pubmed: 12869515