PMID- 25174397
OWN - NLM
STAT- MEDLINE
DCOM- 20151001
LR  - 20211021
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 34
IP  - 27
DP  - 2015 Jul
TI  - CIP4 promotes lung adenocarcinoma metastasis and is associated with poor 
      prognosis.
PG  - 3527-35
LID - 10.1038/onc.2014.280 [doi]
AB  - Aberrant epidermal growth factor receptor (EGFR) signaling in non-small cell lung 
      cancer (NSCLC) is linked to tumor progression, metastasis and poor survival 
      rates. Here we report the role of Cdc42-interacting protein 4 (CIP4) in the 
      regulation of NSCLC cell invasiveness and tumor metastasis. CIP4 was highly 
      expressed in a panel of NSCLC cell lines and normal lung epithelial cell lines. 
      Stable knockdown (KD) of CIP4 in lung adenocarcinoma H1299 cells, expressing 
      wild-type EGFR, led to increased EGFR levels on the cell surface and defects in 
      sustained activation of Erk kinase in H1299 cells treated with EGF. CIP4 
      localized to leading edge projections in NSCLC cells, and CIP4 KD cells displayed 
      defects in EGF-induced cell motility and invasion through extracellular matrix. 
      This correlated with reduced expression and activity of matrix 
      metalloproteinase-2 (MMP-2) in CIP4 KD cells compared with control. In xenograft 
      assays, CIP4 silencing had no effect on tumor growth but resulted in significant 
      defects in spontaneous metastases to the lungs from these subcutaneous tumors. 
      This correlated with reduced expression of the Erk target gene Zeb1 and the Zeb1 
      target gene MMP-2 in CIP4 KD tumors compared with control. CIP4 also enhanced 
      rates of metastasis to the liver and lungs in an intrasplenic experimental 
      metastasis model. In human NSCLC tumor sections, CIP4 expression was elevated 
      greater than or equal to twofold in 43% of adenocarcinomas and 32% of squamous 
      carcinomas compared with adjacent normal lung tissues. Analysis of microarray 
      data for NSCLC patients also revealed that high CIP4 transcript levels correlated 
      with reduced overall survival. Together, these results identify CIP4 as a 
      positive regulator of NSCLC metastasis and a potential poor prognostic biomarker 
      in lung adenocarcinoma.
FAU - Truesdell, P
AU  - Truesdell P
AD  - 1] Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada [2] Cancer Biology and Genetics, Queen's Cancer Research 
      Institute, Kingston, Ontario, Canada.
FAU - Ahn, J
AU  - Ahn J
AD  - 1] Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada [2] Cancer Biology and Genetics, Queen's Cancer Research 
      Institute, Kingston, Ontario, Canada.
FAU - Chander, H
AU  - Chander H
AD  - 1] Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada [2] Cancer Biology and Genetics, Queen's Cancer Research 
      Institute, Kingston, Ontario, Canada.
FAU - Meens, J
AU  - Meens J
AD  - 1] Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada [2] Cancer Biology and Genetics, Queen's Cancer Research 
      Institute, Kingston, Ontario, Canada.
FAU - Watt, K
AU  - Watt K
AD  - 1] Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada [2] Cancer Biology and Genetics, Queen's Cancer Research 
      Institute, Kingston, Ontario, Canada.
FAU - Yang, X
AU  - Yang X
AD  - Department of Pathology and Molecular Medicine, Queen's University, Kingston, 
      Ontario, Canada.
FAU - Craig, A W B
AU  - Craig AW
AD  - 1] Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario, Canada [2] Cancer Biology and Genetics, Queen's Cancer Research 
      Institute, Kingston, Ontario, Canada.
LA  - eng
GR  - 119562-1/Canadian Institutes of Health Research/Canada
GR  - MOP119562/CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140901
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (TRIP10 protein, human)
SB  - IM
MH  - Adenocarcinoma/*diagnosis/genetics/mortality/*pathology
MH  - Adenocarcinoma of Lung
MH  - Aged
MH  - Animals
MH  - Biomarkers, Tumor/physiology
MH  - Carcinoma, Non-Small-Cell Lung/diagnosis/genetics/mortality/pathology
MH  - Cells, Cultured
MH  - Humans
MH  - Lung Neoplasms/*diagnosis/genetics/mortality/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Microtubule-Associated Proteins/*physiology
MH  - Middle Aged
MH  - Minor Histocompatibility Antigens
MH  - Neoplasm Metastasis
MH  - Prognosis
MH  - Survival Analysis
PMC - PMC4978543
MID - CAMS4591
OID - NLM: CAMS4591
COIS- CONFLICT OF INTEREST The authors declare no conflicts of interest.
EDAT- 2014/09/02 06:00
MHDA- 2015/10/02 06:00
PMCR- 2016/08/09
CRDT- 2014/09/02 06:00
PHST- 2013/08/30 00:00 [received]
PHST- 2014/07/21 00:00 [revised]
PHST- 2014/07/23 00:00 [accepted]
PHST- 2014/09/02 06:00 [entrez]
PHST- 2014/09/02 06:00 [pubmed]
PHST- 2015/10/02 06:00 [medline]
PHST- 2016/08/09 00:00 [pmc-release]
AID - onc2014280 [pii]
AID - 10.1038/onc.2014.280 [doi]
PST - ppublish
SO  - Oncogene. 2015 Jul;34(27):3527-35. doi: 10.1038/onc.2014.280. Epub 2014 Sep 1.