PMID- 31214512
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 9
DP  - 2019
TI  - The MAP3K7-mTOR Axis Promotes the Proliferation and Malignancy of Hepatocellular 
      Carcinoma Cells.
PG  - 474
LID - 10.3389/fonc.2019.00474 [doi]
LID - 474
AB  - Targeted therapy is currently limited for patients with hepatocellular carcinoma 
      (HCC) due to the lack of suitable targets. Kinases play pivotal roles in many 
      cellular biological processes, whereas dysregulation of kinases may lead to 
      various diseases, particularly cancer. However, the role of kinases in HCC 
      malignancy remains unclear. In this study, we employed a kinome small interfering 
      RNA (siRNA) library, comprising 710 kinase-related genes, to screen whether any 
      kinases were essential for cell proliferation in various HCC cell lines. Through 
      a kinome siRNA library screening, we found that MAP3K7 was a crucial gene for HCC 
      cell proliferation. Pharmacological or genetic ablation of MAP3K7 diminished the 
      growth, migration, and invasion of HCC cells, including primary HCC cells. Stable 
      knockdown of MAP3K7 attenuated tumor formation in a spheroid cell culture model 
      and tumor xenograft mouse model. In addition, silencing MAP3K7 reduced the 
      phosphorylation and expression of mammalian target of rapamycin (mTOR) in HCC 
      cells. MAP3K7 expression was positively correlated with mTOR expression in tumors 
      of patients with HCC. Higher co-expression of MAP3K7 and mTOR was significantly 
      associated with poor prognosis of HCC. Taken together, our results revealed that 
      the MAP3K7-mTOR axis might promote tumorigenesis and malignancy, which provides a 
      potential marker or therapeutic target for HCC patients.
FAU - Cheng, Jin-Shiung
AU  - Cheng JS
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
FAU - Tsai, Wei-Lun
AU  - Tsai WL
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
AD  - School of Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Liu, Pei-Feng
AU  - Liu PF
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
FAU - Goan, Yih-Gang
AU  - Goan YG
AD  - Division of Thoracic Surgery, Department of Surgery, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
FAU - Lin, Chih-Wen
AU  - Lin CW
AD  - Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou 
      University, Kaohsiung, Taiwan.
AD  - School of Medicine for International Students, I-Shou University, Kaohsiung, 
      Taiwan.
FAU - Tseng, Ho-Hsing
AU  - Tseng HH
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
FAU - Lee, Cheng-Hsin
AU  - Lee CH
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
FAU - Shu, Chih-Wen
AU  - Shu CW
AD  - School of Medicine for International Students, I-Shou University, Kaohsiung, 
      Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20190604
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC6558008
OTO - NOTNLM
OT  - MAP3K7
OT  - invasion
OT  - kinome siRNA library screening
OT  - mTOR
OT  - migration
OT  - prognosis
OT  - proliferation
EDAT- 2019/06/20 06:00
MHDA- 2019/06/20 06:01
PMCR- 2019/01/01
CRDT- 2019/06/20 06:00
PHST- 2019/02/05 00:00 [received]
PHST- 2019/05/17 00:00 [accepted]
PHST- 2019/06/20 06:00 [entrez]
PHST- 2019/06/20 06:00 [pubmed]
PHST- 2019/06/20 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2019.00474 [doi]
PST - epublish
SO  - Front Oncol. 2019 Jun 4;9:474. doi: 10.3389/fonc.2019.00474. eCollection 2019.