PMID- 23824605
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20220410
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 73
IP  - 14
DP  - 2013 Oct
TI  - TMEFF2 and SARDH cooperate to modulate one-carbon metabolism and invasion of 
      prostate cancer cells.
PG  - 1561-75
LID - 10.1002/pros.22706 [doi]
AB  - BACKGROUND: The transmembrane protein with epidermal growth factor and two 
      follistatin motifs, TMEFF2, has been implicated in prostate cancer but its role 
      in this disease is unclear. We recently demonstrated that the tumor suppressor 
      role of TMEFF2 correlates, in part, with its ability to interact with sarcosine 
      dehydrogenase (SARDH) and modulate sarcosine level. TMEFF2 overexpression 
      inhibits sarcosine-induced invasion. Here, we further characterize the functional 
      interaction between TMEFF2 and SARDH and their link with one-carbon (1-C) 
      metabolism and invasion. METHODS: RNA interference was used to study the effect 
      of SARDH and/or TMEFF2 knockdown (KD) in invasion, evaluated using Boyden 
      chambers. The dependence of invasion on 1-C metabolism was determined by 
      examining sensitivity to methotrexate. Real-time PCR and Western blot of 
      subcellular fractions were used to study the effect of SARDH KD or TMEFF2 KD on 
      expression of enzymes involved in one-carbon (1-C) metabolism and on TMEFF2 
      expression and localization. Protein interactions were analyzed by mass 
      spectrometry. Cell viability and proliferation were measured by cell counting and 
      MTT analysis. RESULTS: While knocking down SARDH affects TMEFF2 subcellular 
      localization, this effect is not responsible for the increased invasion observed 
      in SARDH KD cells. Importantly, SARDH and/or TMEFF2 KD promote increased cellular 
      invasion, sensitize the cell to methotrexate, render the cell resistant to 
      invasion induced by sarcosine, a metabolite from the folate-mediated 1-C 
      metabolism pathway, and affect the expression level of enzymes involved in that 
      pathway. CONCLUSIONS: Our findings define a role for TMEFF2 and the 
      folate-mediated 1-C metabolism pathway in modulating cellular invasion.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Green, Thomas
AU  - Green T
AD  - Department of Oncology, Brody School of Medicine at East Carolina University, 
      Greenville, North Carolina, USA.
FAU - Chen, Xiaofei
AU  - Chen X
FAU - Ryan, Stephen
AU  - Ryan S
FAU - Asch, Adam S
AU  - Asch AS
FAU - Ruiz-Echevarria, Maria J
AU  - Ruiz-Echevarria MJ
LA  - eng
GR  - R15 CA155873/CA/NCI NIH HHS/United States
GR  - 1R15CA155873/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130703
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (TMEFF2 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 7440-44-0 (Carbon)
RN  - EC 1.5.8.3 (SARDH protein, human)
RN  - EC 1.5.8.3 (Sarcosine Dehydrogenase)
RN  - YL5FZ2Y5U1 (Methotrexate)
RN  - Z711V88R5F (Sarcosine)
SB  - IM
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Carbon/*metabolism
MH  - Cell Proliferation/drug effects
MH  - Cell Transformation, Neoplastic/drug effects/metabolism
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - *Membrane Proteins/genetics/metabolism
MH  - Methotrexate/pharmacology
MH  - Neoplasm Invasiveness/*genetics
MH  - *Neoplasm Proteins/genetics/metabolism
MH  - *Prostate/metabolism/pathology
MH  - *Prostatic Neoplasms/genetics/metabolism/pathology
MH  - Sarcosine/metabolism
MH  - *Sarcosine Dehydrogenase/genetics/metabolism
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/metabolism
PMC - PMC3878307
MID - NIHMS539608
OTO - NOTNLM
OT  - cellular invasion
OT  - metabolism
OT  - prostate cancer
OT  - tissue culture
COIS- The authors declare no conflict of interest.
EDAT- 2013/07/05 06:00
MHDA- 2014/01/01 06:00
PMCR- 2014/10/01
CRDT- 2013/07/05 06:00
PHST- 2013/01/25 00:00 [received]
PHST- 2013/06/11 00:00 [accepted]
PHST- 2013/07/05 06:00 [entrez]
PHST- 2013/07/05 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 10.1002/pros.22706 [doi]
PST - ppublish
SO  - Prostate. 2013 Oct;73(14):1561-75. doi: 10.1002/pros.22706. Epub 2013 Jul 3.