KBTBD7 promotes non-small cell lung carcinoma progression by enhancing ubiquitin-dependent degradation of PTEN.
Humans
Carcinoma, Non-Small-Cell Lung
/ pathology
Lung Neoplasms
/ pathology
Phosphatidylinositol 3-Kinases
/ metabolism
Ubiquitin
/ metabolism
PTEN Phosphohydrolase
/ genetics
Signal Transduction
Cell Proliferation
Cell Line, Tumor
Cell Movement
Gene Expression Regulation, Neoplastic
rho-Associated Kinases
/ metabolism
Intracellular Signaling Peptides and Proteins
/ metabolism
PTEN
epidermal growth factor
invasion
non-small cell lung cancer
proliferation
the Kelch repeat and BTB domain containing 7
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
12
03
2022
received:
05
12
2021
accepted:
01
04
2022
pubmed:
3
5
2022
medline:
15
12
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
The Kelch repeat and BTB domain containing 7 (KBTBD7) was first cloned in 2010. Its function as a transcriptional activator and a substrate adaptor during the ubiquitination process was soon found. KBTBD7 was shown to be involved in excessive inflammation after myocardial infarction, brain development, and neurofibromin stability. However, studies on the role of KBTBD7 in solid tumors, especially lung cancer, are still lacking. Therefore, in this study, we investigate the role of KBTBD7 in non-small cell lung cancer (NSCLC). Immunohistochemical staining of 104 paired NSCLC and peritumoral normal specimens indicated that KBTBD7 was highly expressed in NSCLC tissues and positively correlated with the histological type, P-TNM stage, lymph node metastasis, and tumor size. KBTBD7 was also well-expressed in NSCLC cell lines, and downregulation of KBTBD7 resulted in inhibition of NSCLC cell proliferation and invasion. Further investigation showed that KBTBD7 enhanced ubiquitin-dependent degradation of PTEN, thus activating EGFR/PI3K/AKT signaling and promoting NSCLC cell proliferation and invasion by regulating CCNE1, CDK4, P27, ZEB-1, Claudin-1, ROCK1, MMP-9, and E-cadherin protein levels. Our results indicate that KBTBD7 may be a potential therapeutic target for the treatment of NSCLC.
Identifiants
pubmed: 35499228
doi: 10.1002/cam4.4794
pmc: PMC9741964
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Ubiquitin
0
PTEN Phosphohydrolase
EC 3.1.3.67
ROCK1 protein, human
EC 2.7.11.1
rho-Associated Kinases
EC 2.7.11.1
PTEN protein, human
EC 3.1.3.67
KBTBD7 protein, human
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4544-4554Informations de copyright
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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