PMID- 30431081
OWN - NLM
STAT- MEDLINE
DCOM- 20190314
LR  - 20211201
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 54
IP  - 1
DP  - 2019 Jan
TI  - DOK7V1 influences the malignant phenotype of lung cancer cells through 
      PI3K/AKT/mTOR and FAK/paxillin signaling pathways.
PG  - 381-389
LID - 10.3892/ijo.2018.4624 [doi]
AB  - Downstream of tyrosine kinase 7 transcript variant 1 (DOK7V1) is a docking 
      protein mediating signal transduction between receptors and intracellular 
      downstream molecules. Our previous study indicated that DOK7V1 was decreased in 
      lung cancer and its lower expression was associated with a decreased survival 
      rate. The 5‑year overall survival rate for patients with lung cancer was 
      20.2 and 18.6% for high and low DOK7 expression, respectively; the 5‑year 
      disease‑free survival rate for patients with lung cancer was 14.3 and 16.9% for 
      high and low DOK7 expression, respectively. DOK7V1 inhibited proliferation and 
      migration, but enhanced adhesion, of lung cancer cells. In the present study, the 
      effect of DOK7V1 and its domains [pleckstrin homology (PH) and 
      phosphotyrosine‑binding (PTB) domain] on the malignant phenotype and associated 
      signaling pathway in lung cancer cells was investigated. The results indicated 
      that truncation of DOK7V1 domains (DOK7V1Delta‑PH and DOK7V1Delta‑PTB) inhibited the 
      proliferation and migration of lung cancer cells which exhibited the same trend 
      as DOK7V1, whereas DOK7V1Delta‑PH and DOK7V1Delta‑PTB exhibited different functions from 
      those of DOK7V1 in cell matrix adhesion. Consistently, DOK7V1 overexpression in 
      lung cancer cells suppressed the phosphoinositide 3‑kinase (PI3K)/protein kinase 
      B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways, but activated 
      the focal adhesion kinase (FAK)/paxillin signaling pathway. Taken together, these 
      results indicate that DOK7V1 may inhibit proliferation and migration via 
      negatively regulating the PI3K/AKT/mTOR signaling pathway, and increase adhesion 
      by upregulating the FAK/paxillin signaling pathway in lung cancer cells.
FAU - Zhao, Huishan
AU  - Zhao H
AD  - Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of 
      Qingdao University, Yantai, Shandong 264000, P.R. China.
FAU - Chen, Gang
AU  - Chen G
AD  - Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing 100039, P.R. 
      China.
FAU - Ye, Lin
AU  - Ye L
AD  - Cardiff‑China Medical Research Collaborative, Cardiff University School of 
      Medicine, Cardiff CF14 4XN, UK.
FAU - Yu, Hefen
AU  - Yu H
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Capital Medical University, Beijing100069, P.R. China.
FAU - Li, Shenglan
AU  - Li S
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Capital Medical University, Beijing100069, P.R. China.
FAU - Jiang, Wen G
AU  - Jiang WG
AD  - Cardiff‑China Medical Research Collaborative, Cardiff University School of 
      Medicine, Cardiff CF14 4XN, UK.
LA  - eng
PT  - Journal Article
DEP - 20181105
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (DOK7 protein, human)
RN  - 0 (Muscle Proteins)
RN  - 0 (Paxillin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - A549 Cells
MH  - *Alternative Splicing
MH  - Cell Line, Tumor
MH  - *Down-Regulation
MH  - Focal Adhesion Protein-Tyrosine Kinases/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/*genetics/metabolism
MH  - Muscle Proteins/*genetics/metabolism
MH  - Paxillin/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - Survival Analysis
OTO - NOTNLM
OT  - downstream of tyrosine kinase 7
OT  - phosphotyrosinebinding domain
OT  - pleckstrin homology domain
OT  - proliferation
OT  - AKT
OT  - FAK
EDAT- 2018/11/16 06:00
MHDA- 2019/03/15 06:00
CRDT- 2018/11/16 06:00
PHST- 2018/06/28 00:00 [received]
PHST- 2018/10/19 00:00 [accepted]
PHST- 2018/11/16 06:00 [pubmed]
PHST- 2019/03/15 06:00 [medline]
PHST- 2018/11/16 06:00 [entrez]
AID - 10.3892/ijo.2018.4624 [doi]
PST - ppublish
SO  - Int J Oncol. 2019 Jan;54(1):381-389. doi: 10.3892/ijo.2018.4624. Epub 2018 Nov 5.