PMID- 34691251
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211026
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Print)
IS  - 1792-1074 (Linking)
VI  - 22
IP  - 6
DP  - 2021 Dec
TI  - KLK6 mediates stemness and metabolism of gastric carcinoma cells via the 
      PI3K/AKT/mTOR signaling pathway.
PG  - 824
LID - 10.3892/ol.2021.13085 [doi]
LID - 824
AB  - Gastric cancer is a common tumor of the digestive system, which can occur in any 
      part of the stomach. Kallikrein 6 (KLK6) is a trypsin-like serine protease and 
      has been found to be involved in extracellular matrix remodeling, tumor invasion 
      and nervous system plasticity. Our previous study reported that KLK6 suppressed 
      HGC-27 gastric cancer cell growth by inhibiting epithelial-mesenchymal 
      transition; however, the mechanism of action underlying the effect of KLK6 still 
      remains unclear. The aim of the present study was to investigate the effect and 
      the underlying mechanism of KLK6 on stem cell-like properties and metabolism in 
      gastric carcinoma cells. The HGC-27 cell line was transfected with KLK6 
      overexpression (OV-KLK6) and interference (short hairpin-KLK6) vectors, then the 
      transfection efficiency was confirmed using western blot analysis and reverse 
      transcription-quantitative PCR. The percentage of CD133(+) and CD44(+) cells was 
      detected using flow cytometry, while the protein expression levels of the 
      stem-associated genes, Nanog, Oct-4, SOX2 and Notch1, the metabolic markers, 
      hexokinase (HK)1, HK2, GLUT1, and the proteins within the PI3K signaling pathway, 
      phosphorylated (p)-PI3K, p-AKT and p-mTOR, were determined using western blot 
      analysis. Biochemical kits were used to measure ATP production, lactic acid 
      content and glucose uptake. A tumorigenicity assay was performed with nude mice 
      to detect gastric tumor volume, and the protein expression level of Oct-4, Nanog, 
      HK1, HK2 and GLUT1, and the mRNA expression level of KLK6 was also determined in 
      gastric tumor tissues of mice. Compared with that in the control group, KLK6 
      protein and mRNA expression levels were significantly decreased in the four 
      sh-RNA groups (P<0.05). Among them, sh-RNA-3 induced the lowest KLK6 expression 
      and was used to silence KLK6 in subsequent experiments. Compared with that in the 
      control and negative control groups, the percentage of CD133(+) and CD44(+) 
      cells, the protein expression level of Oct-4, Nanog, HK1, HK2, GLUT1, p-PI3K, 
      p-AKT and p-mTOR, and ATP content, lactic acid production, glucose uptake and 
      gastric tumor volume were significantly decreased by sh-KLK6 (P<0.05), whereas 
      KLK6 overexpression induced the opposite effect (P<0.05). In conclusion, KLK6 
      modulated stemness properties and cell metabolic profile in gastric carcinoma 
      cells and the mechanism may be associated with the PI3K/AKT/mTOR signaling 
      pathway.
CI  - Copyright (c) 2021, Spandidos Publications.
FAU - Zhou, Dong
AU  - Zhou D
AD  - Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei 
      Medical College, Xiangyang, Hubei 441000, P.R. China.
FAU - He, Yanping
AU  - He Y
AD  - Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei 
      Medical College, Xiangyang, Hubei 441000, P.R. China.
FAU - Li, Hengping
AU  - Li H
AD  - Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei 
      Medical College, Xiangyang, Hubei 441000, P.R. China.
FAU - Huang, Weidong
AU  - Huang W
AD  - Department of Vascular Surgery, First People's Hospital of Xiangyang City, Hubei 
      Medical College, Xiangyang, Hubei 441000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20211012
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC8527834
OTO - NOTNLM
OT  - KLK6
OT  - PI3K/AKT/mTOR
OT  - gastric carcinoma cells
OT  - metabolism
OT  - stemness
COIS- The authors declare that they have no competing interests.
EDAT- 2021/10/26 06:00
MHDA- 2021/10/26 06:01
PMCR- 2021/10/12
CRDT- 2021/10/25 06:27
PHST- 2020/05/28 00:00 [received]
PHST- 2021/04/23 00:00 [accepted]
PHST- 2021/10/25 06:27 [entrez]
PHST- 2021/10/26 06:00 [pubmed]
PHST- 2021/10/26 06:01 [medline]
PHST- 2021/10/12 00:00 [pmc-release]
AID - OL-0-0-13085 [pii]
AID - 10.3892/ol.2021.13085 [doi]
PST - ppublish
SO  - Oncol Lett. 2021 Dec;22(6):824. doi: 10.3892/ol.2021.13085. Epub 2021 Oct 12.