PMID- 31261148
OWN - NLM
STAT- MEDLINE
DCOM- 20210215
LR  - 20211204
IS  - 1423-0194 (Electronic)
IS  - 0028-3835 (Linking)
VI  - 110
IP  - 3-4
DP  - 2020
TI  - STK33 Promotes the Growth and Progression of Human Pancreatic Neuroendocrine 
      Tumour via Activation of the PI3K/AKT/mTOR Pathway.
PG  - 307-320
LID - 10.1159/000501829 [doi]
AB  - BACKGROUND: Serine/threonine kinase 33 (STK33) has been reported to play an 
      important role in cancer cell proliferation. We investigated the role of STK33 in 
      pancreatic neuroendocrine tumour (PNET) and the underlying mechanisms. METHODS: 
      PNET specimens and adjacent non-tumorous pancreatic tissues from 84 patients who 
      underwent curative surgery for PNET were stained by immunochemistry for STK33. 
      The relationships among STK33 expression, clinicopathological parameters and 
      clinical prognosis were statistically analysed. MTT, scratching, Transwell and 
      apoptosis assays were employed to detect the effects of STK33 knockdown (siSTK33) 
      or STK33 overexpression (pSTK33) on major oncogenic properties of cells of 2 PNET 
      cell lines (BON and QGP-1), and real-time PCR and western blot were used to 
      examine the expression of relevant genes. RESULTS: Relative to its expression in 
      normal pancreatic tissue, STK33 was overexpressed in PNET specimens. Furthermore, 
      STK33 expression was significantly associated with World Health Organization 
      classification (p < 0.001), American Joint Committee on Cancer stage (p < 0.001), 
      lymph node metastasis (p < 0.001), tumour size (p = 0.022), sex (p = 0.003), 
      perineural invasion (p < 0.001) and shorter disease-free survival of patients 
      with PNET (p < 0.001). Enforced STK33 expression promoted PNET cell 
      proliferation, migration and invasion and tumour growth and inhibited cell 
      apoptosis, whereas STK33 depletion exerted the opposite effects. Mechanistic 
      studies revealed that STK33 promoted growth and progression of PNET via 
      activation of the phosphotidylinositol-3-kinase (PI3K)/AKT/mammalian target of 
      rapamycin (mTOR) pathway. CONCLUSIONS: STK33 plays important roles in the tumour 
      growth and progression of PNET via activation of the PI3K/AKT/mTOR pathway and 
      has potential as a therapeutic target to improve PNET treatment.
CI  - (c) 2019 S. Karger AG, Basel.
FAU - Zhou, Bo
AU  - Zhou B
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China, 
      1509004@zju.edu.cn.
FAU - Xiang, Jie
AU  - Xiang J
AD  - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First 
      Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Zhan, Canyang
AU  - Zhan C
AD  - Department of Neonatology, Children's Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China.
FAU - Liu, Jianhua
AU  - Liu J
AD  - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First 
      Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Yan, Sheng
AU  - Yan S
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190702
PL  - Switzerland
TA  - Neuroendocrinology
JT  - Neuroendocrinology
JID - 0035665
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (STK33 protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Disease Progression
MH  - Humans
MH  - Neuroendocrine Tumors/*metabolism/*pathology
MH  - Pancreatic Neoplasms/*metabolism/*pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - PI3K/AKT/mTOR pathway
OT  - Pancreatic neuroendocrine tumour
OT  - Progression
OT  - Serine/threonine kinase 33
EDAT- 2019/07/02 06:00
MHDA- 2021/02/16 06:00
CRDT- 2019/07/02 06:00
PHST- 2019/03/24 00:00 [received]
PHST- 2019/06/28 00:00 [accepted]
PHST- 2019/07/02 06:00 [pubmed]
PHST- 2021/02/16 06:00 [medline]
PHST- 2019/07/02 06:00 [entrez]
AID - 000501829 [pii]
AID - 10.1159/000501829 [doi]
PST - ppublish
SO  - Neuroendocrinology. 2020;110(3-4):307-320. doi: 10.1159/000501829. Epub 2019 Jul 
      2.