PMID- 25381040
OWN - NLM
STAT- MEDLINE
DCOM- 20150401
LR  - 20181202
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 29
IP  - 2
DP  - 2015 Feb
TI  - EGFR and IGF-1R in regulation of prostate cancer cell phenotype and polarity: 
      opposing functions and modulation by T-cadherin.
PG  - 494-507
LID - 10.1096/fj.14-249367 [doi]
AB  - T-cadherin is an atypical glycosylphosphatidylinsoitol-anchored member of the 
      cadherin superfamily of adhesion molecules. We found that T-cadherin 
      overexpression in malignant (DU145) and benign (BPH-1) prostatic epithelial cell 
      lines or silencing in the BPH-1 cell line, respectively, promoted or inhibited 
      migration and spheroid invasion in collagen I gel and Matrigel. 
      T-cadherin-dependent effects were associated with changes in cell phenotype: 
      overexpression caused cell dissemination and loss of polarity evaluated by 
      relative positioning of the Golgi/nuclei in cell groups, whereas silencing caused 
      formation of compact polarized epithelial-like clusters. Epidermal growth factor 
      receptor (EGFR) and IGF factor-1 receptor (IGF-1R) were identified as mediators 
      of T-cadherin effects. These receptors per se had opposing influences on cell 
      phenotype. EGFR activation with EGF or IGF-1R inhibition with NVP-AEW541 promoted 
      dissemination, invasion, and polarity loss. Conversely, inhibition of EGFR with 
      gefitinib or activation of IGF-1R with IGF-1 rescued epithelial morphology and 
      decreased invasion. T-cadherin silencing enhanced both EGFR and IGF-1R 
      phosphorylation, yet converted cells to the morphology typical for activated 
      IGF-1R. T-cadherin effects were sensitive to modulation of EGFR or IGF-1R 
      activity, suggesting direct involvement of both receptors. We conclude that 
      T-cadherin regulates prostate cancer cell behavior by tuning the balance in 
      EGFR/IGF-1R activity and enhancing the impact of IGF-1R.
CI  - (c) FASEB.
FAU - Maslova, Kseniya
AU  - Maslova K
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Kyriakakis, Emmanouil
AU  - Kyriakakis E
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Pfaff, Dennis
AU  - Pfaff D
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Frachet, Audrey
AU  - Frachet A
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Frismantiene, Agne
AU  - Frismantiene A
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Bubendorf, Lukas
AU  - Bubendorf L
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Ruiz, Christian
AU  - Ruiz C
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Vlajnic, Tatjana
AU  - Vlajnic T
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Erne, Paul
AU  - Erne P
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
FAU - Resink, Therese J
AU  - Resink TJ
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland therese-j.resink@unibas.ch.
FAU - Philippova, Maria
AU  - Philippova M
AD  - *Department of Biomedicine, Laboratory for Signal Transduction, and Institute of 
      Pathology, University Hospital Basel, University of Basel, Basel, Switzerland; 
      and Hirslanden Klinik St. Anna, Luzern, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141107
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Cadherins)
RN  - 0 (Drug Combinations)
RN  - 0 (H-cadherin)
RN  - 0 (Laminin)
RN  - 0 (NVP-AEW541)
RN  - 0 (Proteoglycans)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (Quinazolines)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Cadherins/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Nucleus/metabolism
MH  - Cell Survival
MH  - Collagen/chemistry
MH  - Drug Combinations
MH  - ErbB Receptors/*metabolism
MH  - Gefitinib
MH  - Gene Silencing
MH  - Golgi Apparatus/metabolism
MH  - Humans
MH  - Laminin/chemistry
MH  - Male
MH  - Neoplasm Invasiveness
MH  - Phenotype
MH  - Phosphorylation
MH  - Prostate/*metabolism
MH  - Prostatic Neoplasms/*metabolism
MH  - Proteoglycans/chemistry
MH  - Pyrimidines/chemistry
MH  - Pyrroles/chemistry
MH  - Quinazolines/chemistry
MH  - Receptor, IGF Type 1/*metabolism
OTO - NOTNLM
OT  - NVP-AEW541
OT  - gefitinib
OT  - malignant and benign prostate epithelial cell lines
EDAT- 2014/11/09 06:00
MHDA- 2015/04/02 06:00
CRDT- 2014/11/09 06:00
PHST- 2014/11/09 06:00 [entrez]
PHST- 2014/11/09 06:00 [pubmed]
PHST- 2015/04/02 06:00 [medline]
AID - fj.14-249367 [pii]
AID - 10.1096/fj.14-249367 [doi]
PST - ppublish
SO  - FASEB J. 2015 Feb;29(2):494-507. doi: 10.1096/fj.14-249367. Epub 2014 Nov 7.