Analysis of the Protein-Protein Interaction Network Identifying c-Met as a Target of Gigantol in the Suppression of Lung Cancer Metastasis.
Gigantol
PI3K
c-Met
lung cancer
metastasis
proteomics
Journal
Cancer genomics & proteomics
ISSN: 1790-6245
Titre abrégé: Cancer Genomics Proteomics
Pays: Greece
ID NLM: 101188791
Informations de publication
Date de publication:
Historique:
received:
02
02
2021
revised:
03
03
2021
accepted:
17
03
2021
entrez:
24
4
2021
pubmed:
25
4
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
c-Met (mesenchymal-epithelial transition factor) facilitates cancer progression and is recognized as a promising drug target. The molecular target of gigantol from Dendrobium draconis in suppressing cancer metastasis is largely unknown. Proteins affected by gigantol treatment were subjected to proteomic and bioinformatic analysis. Protein-Protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes (STRING). The Kyoto Encyclopedia of Genes and Genomes (KEGG) database and hub gene were used to enrich the dominant pathways. Western blot analysis and immunofluorescence were used to validate the effect of gigantol on the target protein and signaling. Gigantol down-regulates 41 adhesion proteins and 39-migratory proteins, while it up-regulates 30 adhesion-related proteins and 22 proteins controlling cell migration. The key components of our constructed PPI network comprised 41 proteins of cell adhesion enriched in 40 nodes with 25 edges, 39 proteins of cell migration enriched in 39 nodes with 76 edges in down-regulated proteins, 30 proteins of cell adhesion enriched in 30 nodes with 21 edges, and 22 proteins of cell migration enriched in 22 nodes with 22 edges in up-regulated protein. c-Met was identified as a central protein of the PPI network in the largest degree. KEGG mapper further suggested that c-Met, PI3K, and AKT were the regulatory proteins affected by gigantol. To confirm, the effects of gigantol on c-Met, the p-PI3K, PI3K, p-AKT, and AKT proteins were investigated by western blotting and the results showed a consistent effect of gigantol in the suppression of the c-Met/PI3K/AKT signal. Next, immunofluorescence showed a dramatic decrease in c-Met, PI3K and AKT activation in response to gigantol. c-Met is an important target of gigantol treatment in lung cancer cells. Gigantol suppresses metastasis-related cell motility through decreasing c-Met resulting in PI3K/AKT signaling disruption.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
c-Met (mesenchymal-epithelial transition factor) facilitates cancer progression and is recognized as a promising drug target. The molecular target of gigantol from Dendrobium draconis in suppressing cancer metastasis is largely unknown.
MATERIALS AND METHODS
METHODS
Proteins affected by gigantol treatment were subjected to proteomic and bioinformatic analysis. Protein-Protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes (STRING). The Kyoto Encyclopedia of Genes and Genomes (KEGG) database and hub gene were used to enrich the dominant pathways. Western blot analysis and immunofluorescence were used to validate the effect of gigantol on the target protein and signaling.
RESULTS
RESULTS
Gigantol down-regulates 41 adhesion proteins and 39-migratory proteins, while it up-regulates 30 adhesion-related proteins and 22 proteins controlling cell migration. The key components of our constructed PPI network comprised 41 proteins of cell adhesion enriched in 40 nodes with 25 edges, 39 proteins of cell migration enriched in 39 nodes with 76 edges in down-regulated proteins, 30 proteins of cell adhesion enriched in 30 nodes with 21 edges, and 22 proteins of cell migration enriched in 22 nodes with 22 edges in up-regulated protein. c-Met was identified as a central protein of the PPI network in the largest degree. KEGG mapper further suggested that c-Met, PI3K, and AKT were the regulatory proteins affected by gigantol. To confirm, the effects of gigantol on c-Met, the p-PI3K, PI3K, p-AKT, and AKT proteins were investigated by western blotting and the results showed a consistent effect of gigantol in the suppression of the c-Met/PI3K/AKT signal. Next, immunofluorescence showed a dramatic decrease in c-Met, PI3K and AKT activation in response to gigantol.
CONCLUSION
CONCLUSIONS
c-Met is an important target of gigantol treatment in lung cancer cells. Gigantol suppresses metastasis-related cell motility through decreasing c-Met resulting in PI3K/AKT signaling disruption.
Identifiants
pubmed: 33893079
pii: 18/3/261
doi: 10.21873/cgp.20257
pmc: PMC8126329
doi:
Substances chimiques
Bibenzyls
0
gigantol
67884-30-4
Guaiacol
6JKA7MAH9C
MET protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
261-272Informations de copyright
Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Références
J Natl Cancer Inst. 2011 Apr 20;103(8):645-61
pubmed: 21464397
Cancer Treat Rev. 2017 Nov;60:1-11
pubmed: 28843992
Breast Cancer Res Treat. 2011 Jul;128(1):7-21
pubmed: 21499686
Tumour Biol. 2014 Sep;35(9):8483-523
pubmed: 25104089
Oncol Rep. 2017 Feb;37(2):865-870
pubmed: 27959444
CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30
pubmed: 26742998
Evid Based Complement Alternat Med. 2016;2016:4561674
pubmed: 27651818
Prostate. 2016 Dec;76(16):1469-1483
pubmed: 27416770
Genome Res. 2008 Apr;18(4):644-52
pubmed: 18381899
Curr Treat Options Oncol. 2014 Dec;15(4):670-82
pubmed: 25266653
BMC Syst Biol. 2010 May 12;4:60
pubmed: 20462429
Sci Rep. 2015 Feb 16;5:8473
pubmed: 25683757
Nat Rev Cancer. 2010 May;10(5):342-52
pubmed: 20414202
Cancer Genomics Proteomics. 2020 Nov-Dec;17(6):781-793
pubmed: 33099479
J Thorac Oncol. 2010 Mar;5(3):305-13
pubmed: 20107422
Nat Rev Mol Cell Biol. 2010 Dec;11(12):834-48
pubmed: 21102609
J Nat Prod. 2014 Jun 27;77(6):1359-66
pubmed: 24844664
Ther Adv Med Oncol. 2011 Jul;3(4):171-84
pubmed: 21904579
Nat Rev Cancer. 2006 Aug;6(8):637-45
pubmed: 16862193
Nat Rev Cancer. 2011 Jul 22;11(8):573-87
pubmed: 21779009
Curr Biol. 1997 Apr 1;7(4):261-9
pubmed: 9094314
Oncol Lett. 2017 Aug;14(2):2254-2260
pubmed: 28789447
Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25
pubmed: 14685170
Science. 2005 Feb 18;307(5712):1098-101
pubmed: 15718470
Cancer Sci. 2016 Dec;107(12):1867-1876
pubmed: 27779808
Evid Based Complement Alternat Med. 2015;2015:350410
pubmed: 25685168
Mutat Res. 2011 Jul-Oct;728(1-2):23-34
pubmed: 21605699
Evid Based Complement Alternat Med. 2015;2015:836564
pubmed: 26339272
Cytokine Growth Factor Rev. 2002 Feb;13(1):41-59
pubmed: 11750879