NRP2 transcriptionally regulates its downstream effector WDFY1

Samikshan Dutta, Sohini Roy, Navatha S. Polavaram, Gustavo B. Baretton, Michael H. Muders, Surinder Kumar Batra, Kaustubh Datta

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number23588
JournalScientific reports
Volume6
DOIs
StatePublished - Mar 30 2016

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Neuropilin-2
Neuropilins
Neoplasms
Vascular Endothelial Growth Factor Receptor
Membrane Glycoproteins
Autophagy
Cell Survival
Cell Death
Transcription Factors
Clone Cells
Maintenance
Phenotype

ASJC Scopus subject areas

  • General

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NRP2 transcriptionally regulates its downstream effector WDFY1. / Dutta, Samikshan; Roy, Sohini; Polavaram, Navatha S.; Baretton, Gustavo B.; Muders, Michael H.; Batra, Surinder Kumar; Datta, Kaustubh.

In: Scientific reports, Vol. 6, 23588, 30.03.2016.

Research output: Contribution to journalArticle

Dutta S, Roy S, Polavaram NS, Baretton GB, Muders MH, Batra SK et al. NRP2 transcriptionally regulates its downstream effector WDFY1. Scientific reports. 2016 Mar 30;6. 23588. https://doi.org/10.1038/srep23588
Dutta, Samikshan ; Roy, Sohini ; Polavaram, Navatha S. ; Baretton, Gustavo B. ; Muders, Michael H. ; Batra, Surinder Kumar ; Datta, Kaustubh. / NRP2 transcriptionally regulates its downstream effector WDFY1. In: Scientific reports. 2016 ; Vol. 6.
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