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2016 ; 6
(ä): 23588
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NRP2 transcriptionally regulates its downstream effector WDFY1
#MMPMID27026195
Dutta S
; Roy S
; Polavaram NS
; Baretton GB
; Muders MH
; Batra S
; Datta K
Sci Rep
2016[Mar]; 6
(ä): 23588
PMID27026195
show ga
Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors
for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of
NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells,
a function distinctly different from its role as a co-receptor. WD Repeat and
FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this
function. Our results indicated that NRP2 maintains an optimum concentration of
WDFY1 by negatively regulating its expression. Since increased expression of
WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in
metastatic cancer cells to sustain high endocytic activity, essential for
promotion of oncogenic activation and cancer cell survival. Here, we have
delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our
results indicated that NRP2 inhibits WDFY1 transcription by preventing the
nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1
(FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis
has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis
is a critical event in maintaining metastatic phenotype in cancer cells. Thus,
inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce
cell death in metastatic cancer.
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