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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncotarget
2016 ; 7
(45
): 74189-74202
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex
regulating growth and survival of prostate cancer cells "in vitro" and
correlating with progression "in vivo"
#MMPMID27713116
Perico ME
; Grasso S
; Brunelli M
; Martignoni G
; Munari E
; Moiso E
; Fracasso G
; Cestari T
; Naim HY
; Bronte V
; Colombatti M
; Ramarli D
Oncotarget
2016[Nov]; 7
(45
): 74189-74202
PMID27713116
show ga
The expression of Prostate Specific-Membrane Antigen (PSMA) increases in
high-grade prostate carcinoma envisaging a role in growth and progression. We
show here that clustering PSMA at LNCaP or PC3-PSMA cell membrane activates AKT
and MAPK pathways thus promoting proliferation and survival. PSMA activity was
dependent on the assembly of a macromolecular complex including filamin A, beta1
integrin, p130CAS, c-Src and EGFR. Within this complex beta1 integrin became
activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y1086 and
Y1173 EGF-independent residues. Silencing or blocking experiments with drugs
demonstrated that all the complex components were required for full
PSMA-dependent promotion of cell growth and/or survival in 3D culture, but that
p130CAS and EGFR exerted a major role. All PSMA complex components were found
assembled in multiple samples of two high-grade prostate carcinomas and
associated with EGFR phosphorylation at Y1086. The expression of p130CAS and
pEGFRY1086 was thus analysed by tissue micro array in 16 castration-resistant
prostate carcinomas selected from 309 carcinomas and stratified from GS 3+4 to GS
5+5. Patients with Gleason Score ?5 resulted negative whereas those with GS?5
expressed p130CAS and pEGFRY1086 in 75% and 60% of the cases,
respectively.Collectively, our results demonstrate for the first time that PSMA
recruits a functionally active complex which is present in high-grade patients.
In addition, two components of this complex, p130CAS and the novel pEGFRY1086,
correlate with progression in castration-resistant patients and could be
therefore useful in therapeutic or surveillance strategies of these patients.