PMID- 30038287
OWN - NLM
STAT- MEDLINE
DCOM- 20191203
LR  - 20191203
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 8
DP  - 2018 Jul 23
TI  - Overexpression of PEAK1 contributes to epithelial-mesenchymal transition and 
      tumor metastasis in lung cancer through modulating ERK1/2 and JAK2 signaling.
PG  - 802
LID - 10.1038/s41419-018-0817-1 [doi]
LID - 802
AB  - Pseudopodium-enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine 
      kinase, has been demonstrated to act as an oncogenic regulator in breast and 
      pancreatic cancers. However, the role of PEAK1 in the progression and metastasis 
      of lung cancer is still unknown. Here, we observed that ectopic PEAK1 expression 
      promoted lung cancer cell migration and invasion, while PEAK1 knockout resulted 
      in suppressed cell migration and invasion. Interestingly, cell proliferation did 
      not significantly increase or decrease in either the PEAK1 overexpression or 
      knockout groups compared with the corresponding control cells. In addition, PEAK1 
      overexpression could induce epithelial-to-mesenchymal transition (EMT) and the 
      expression of matrix metalloproteinase-2 (MMP2) and MMP9 both in vitro and in 
      vivo, whereas PEAK1 knockout had the opposite effects. Then, we had confirmed 
      that PEAK1 was significantly upregulated in lung cancer tissues, and correlated 
      with a higher tumor node metastasis stage. Moreover, PEAK1 upregulation markedly 
      enhanced the activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and 
      Janus kinase-2 (JAK2) signaling in lung cancer cells. Further work demonstrated 
      that the combination of PD98059 with AZD1480 could reverse the effects of 
      PEAK1-induced EMT, cell migration and invasion. Our findings highlight a newer 
      mechanism for PEAK1 in regulating EMT and metastasis in lung cancer, which might 
      serve as a therapeutic target for lung cancer patients.
FAU - Ding, Chenbo
AU  - Ding C
AD  - Medical School of Southeast University, Nanjing, 210009, China. 
      dcb06296632@163.com.
AD  - Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, 
      Nanjing, 210009, China. dcb06296632@163.com.
FAU - Tang, Wendong
AU  - Tang W
AD  - Medical School of Southeast University, Nanjing, 210009, China.
FAU - Fan, Xiaobo
AU  - Fan X
AD  - Medical School of Southeast University, Nanjing, 210009, China.
FAU - Wang, Xiyong
AU  - Wang X
AD  - Medical School of Southeast University, Nanjing, 210009, China.
FAU - Wu, Hairu
AU  - Wu H
AD  - Medical School of Southeast University, Nanjing, 210009, China.
FAU - Xu, Hongbo
AU  - Xu H
AD  - Medical School of Southeast University, Nanjing, 210009, China.
FAU - Xu, Wei
AU  - Xu W
AD  - Medical School of Southeast University, Nanjing, 210009, China.
FAU - Gao, Wei
AU  - Gao W
AD  - Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, 
      Nanjing, 210009, China.
FAU - Wu, Guoqiu
AU  - Wu G
AD  - Medical School of Southeast University, Nanjing, 210009, China. 
      nationball@163.com.
AD  - Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, 
      Nanjing, 210009, China. nationball@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180723
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Flavonoids)
RN  - EC 2.7.10.1 (PEAK1 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Female
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Janus Kinase 2/antagonists & inhibitors/*metabolism
MH  - Lung Neoplasms/metabolism/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 2/genetics/metabolism
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Signal Transduction
PMC - PMC6056550
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/07/25 06:00
MHDA- 2019/12/04 06:00
PMCR- 2018/07/23
CRDT- 2018/07/25 06:00
PHST- 2018/02/13 00:00 [received]
PHST- 2018/06/25 00:00 [accepted]
PHST- 2018/06/18 00:00 [revised]
PHST- 2018/07/25 06:00 [entrez]
PHST- 2018/07/25 06:00 [pubmed]
PHST- 2019/12/04 06:00 [medline]
PHST- 2018/07/23 00:00 [pmc-release]
AID - 10.1038/s41419-018-0817-1 [pii]
AID - 817 [pii]
AID - 10.1038/s41419-018-0817-1 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Jul 23;9(8):802. doi: 10.1038/s41419-018-0817-1.