Influence of ARHGAP29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells.
Breast Neoplasms
/ metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic
Coculture Techniques
Epithelial-Mesenchymal Transition
Female
GTPase-Activating Proteins
/ metabolism
Humans
MCF-7 Cells
Mesenchymal Stem Cells
Neoplasm Invasiveness
Proto-Oncogene Proteins c-akt
/ metabolism
RNA, Small Interfering
/ metabolism
Signal Transduction
rhoA GTP-Binding Protein
/ metabolism
AKT1
ARHGAP29
EMT
RhoA
breast cancer
invasion
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
05 12 2020
05 12 2020
Historique:
received:
05
10
2020
revised:
18
11
2020
accepted:
03
12
2020
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
10
7
2021
Statut:
epublish
Résumé
Aggressive and mesenchymal-transformed breast cancer cells show high expression levels of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression significantly increased after the induction of mesenchymal transformation in breast cancer cells. Therefore, we investigated the influence of ARHGAP29 on the invasiveness of aggressive and mesenchymal-transformed breast cancer cells. After knock-down of ARHGAP29 using siRNA, invasion of HCC1806, MCF-7-EMT, and T-47D-EMT breast cancer cells was significantly reduced. This could be explained by reduced inhibition of RhoA and a consequent increase in stress fiber formation. Proliferation of the breast cancer cell line T-47D-EMT was slightly increased by reduced expression of ARHGAP29, whereas that of HCC1806 and MCF-7-EMT significantly increased. Using interaction analyses we found that AKT1 is a possible interaction partner of ARHGAP29. Therefore, the expression of AKT1 after siRNA knock-down of ARHGAP29 was tested. Reduced ARHGAP29 expression was accompanied by significantly reduced AKT1 expression. However, the ratio of active pAKT1 to total AKT1 remained unchanged or was significantly increased after ARHGAP29 knock-down. Our results show that ARHGAP29 could be an important factor in the invasion of aggressive and mesenchymal-transformed breast cancer cells. Further research is required to fully understand the underlying mechanisms.
Identifiants
pubmed: 33291460
pii: cells9122616
doi: 10.3390/cells9122616
pmc: PMC7762093
pii:
doi:
Substances chimiques
ARHGAP29 protein, human
0
GTPase-Activating Proteins
0
RNA, Small Interfering
0
RHOA protein, human
124671-05-2
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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