Mammalian STE20‑like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2‑mediated mitophagy.
MST1
pancreatic cancer
Mfn2
mitophagy
apoptosis
Journal
Molecular medicine reports
ISSN: 1791-3004
Titre abrégé: Mol Med Rep
Pays: Greece
ID NLM: 101475259
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
27
11
2019
accepted:
19
03
2020
pubmed:
8
5
2020
medline:
17
2
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Mammalian STE20-like kinase 1 (MST1) plays an important role in pancreatic cancer progression, but its downstream targets are still unknown. In the present study, our results indicated that MST1 expression was significantly downregulated in pancreatic cancer cell lines (PANC‑1, BxPC‑3 and HPAC) compared with that in the normal ductal epithelial cell line (hTERT‑HPNE). Moreover, MST1 overexpression in PANC‑1 cells led to increased apoptosis as determined by MTT and TUNEL assays and inhibited cellular migration. Mechanistically, upregulation of MST1 expression caused mitochondrial dysfunction, decreased ATP production, and activation of the mitochondrial‑dependent apoptotic pathway via inhibition of mitofusin 2 (Mfn2)‑mediated mitophagy, which ultimately resulted in increased cellular apoptosis and decreased cellular migration. Collectively, the present study demonstrated that MST1 may regulate pancreatic cancer PANC‑1 cell survival, invasion and migration through Mfn2‑mediated mitophagy, laying the foundation for the exploration of novel therapeutic targets for pancreatic cancer.
Identifiants
pubmed: 32377725
doi: 10.3892/mmr.2020.11098
pmc: PMC7248474
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Mitochondrial Proteins
0
STK4 protein, human
EC 2.7.1.11
Protein Serine-Threonine Kinases
EC 2.7.11.1
GTP Phosphohydrolases
EC 3.6.1.-
MFN2 protein, human
EC 3.6.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
398-404Références
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