PMID- 27995993
OWN - NLM
STAT- MEDLINE
DCOM- 20180723
LR  - 20220408
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Dec 20
TI  - PRKAR1A is a functional tumor suppressor inhibiting ERK/Snail/E-cadherin pathway 
      in lung adenocarcinoma.
PG  - 39630
LID - 10.1038/srep39630 [doi]
LID - 39630
AB  - Protein Kinase cAMP-Dependent Regulatory Type I Alpha (PRKAR1A) is a 
      tissue-specific extinguisher that transduces a signal through phosphorylation of 
      different target proteins. Loss of PRKAR1A was frequently observed in endocrine 
      neoplasia and stromal cell tumors. However, a few cases were seen in epithelial 
      tumors. Previously, we first found that PRKAR1A was downregulated in lung 
      adenocarcinoma patients. Thus, the present study aimed to clarify its clinical 
      implication and biological function as a tumor suppressor in lung adenocarcinoma. 
      The low levels of PRKAR1A transcript were correlated with tumor progression and 
      poor overall survival. The re-expression of PRKAR1A in H1299 cells suppressed the 
      tumor cell proliferation and migration; stable knockdown (KD) of PRKAR1A in A549 
      cells enhanced this function both in vitro and in vivo. Moreover, KD of PRKAR1A 
      in A549 cells promoted the statistical colonization of circulating tumor cells to 
      the lungs in nude mice. These effects by PRKAR1A were attributed to inhibiting 
      E-cadherin expression. Elevated E-cadherin significantly suppressed the 
      PRKAR1A-KD induced cell proliferation and migration. Most notably, deletion of 
      PRKAR1A inhibited E-cadherin by activating ERK/Snail signaling. In conclusion, 
      PRKAR1A was a potent suppressor, and through the inhibition of 
      PRKAR1A-ERK-Snail-E-cadherin axis could serve as a potential therapeutic target.
FAU - Wang, Shaoqiang
AU  - Wang S
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Xiangya Road 87th, Changsha, 410008, Hunan, P. R. China.
FAU - Cheng, Yuanda
AU  - Cheng Y
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Xiangya Road 87th, Changsha, 410008, Hunan, P. R. China.
FAU - Zheng, Yingying
AU  - Zheng Y
AD  - Department of endocrinology, Xiangya Hospital, Central South University, Xiangya 
      Road 87th, Changsha, 410008, Hunan, P. R. China.
FAU - He, Zhiwei
AU  - He Z
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Xiangya Road 87th, Changsha, 410008, Hunan, P. R. China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Xiangya Road 87th, Changsha, 410008, Hunan, P. R. China.
FAU - Zhou, Wolong
AU  - Zhou W
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Xiangya Road 87th, Changsha, 410008, Hunan, P. R. China.
FAU - Duan, Chaojun
AU  - Duan C
AD  - Institute of Medical Sciences, Key Laboratory of Cancer Proteomics of Chinese 
      Ministry of Health, Xiangya Hospital, Central South University, Xiangya Road 
      87th, Changsha, 410008, Hunan, P. R. China.
FAU - Zhang, Chunfang
AU  - Zhang C
AD  - Department of Thoracic Surgery, Xiangya Hospital, Central South University, 
      Xiangya Road 87th, Changsha, 410008, Hunan, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161220
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antigens, CD)
RN  - 0 (CDH1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cyclic AMP-Dependent Protein Kinase RIalpha Subunit)
RN  - 0 (PRKAR1A protein, human)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snail Family Transcription Factors)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - A549 Cells
MH  - Adenocarcinoma/*metabolism
MH  - Aged
MH  - Animals
MH  - Antigens, CD
MH  - Cadherins/*metabolism
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Snail Family Transcription Factors/*metabolism
MH  - Treatment Outcome
PMC - PMC5171641
EDAT- 2016/12/21 06:00
MHDA- 2018/07/24 06:00
PMCR- 2016/12/20
CRDT- 2016/12/21 06:00
PHST- 2016/05/23 00:00 [received]
PHST- 2016/11/25 00:00 [accepted]
PHST- 2016/12/21 06:00 [entrez]
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2018/07/24 06:00 [medline]
PHST- 2016/12/20 00:00 [pmc-release]
AID - srep39630 [pii]
AID - 10.1038/srep39630 [doi]
PST - epublish
SO  - Sci Rep. 2016 Dec 20;6:39630. doi: 10.1038/srep39630.