Neuropilin-2 Regulates Endosome Maturation and EGFR Trafficking to Support Cancer Cell Pathobiology

Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulato...

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Published inCancer research (Chicago, Ill.) Vol. 76; no. 2; pp. 418 - 428
Main Authors Dutta, Samikshan, Roy, Sohini, Polavaram, Navatha S, Stanton, Marissa J, Zhang, Heyu, Bhola, Tanvi, Hönscheid, Pia, Donohue, Jr, Terrence M, Band, Hamid, Batra, Surinder K, Muders, Michael H, Datta, Kaustubh
Format Journal Article
LanguageEnglish
Published United States 15.01.2016
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Abstract Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface EGFR, arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat- and FYVE-domain-containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies.
AbstractList Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface epidermal growth factor receptor (EGFR), arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat and FYVE-domain-containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies.
Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface EGFR, arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat- and FYVE-domain-containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies.
Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface EGFR, arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat– and FYVE-domain–containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies. Cancer Res; 76(2); 418–28. ©2015 AACR.
Author Stanton, Marissa J
Donohue, Jr, Terrence M
Zhang, Heyu
Muders, Michael H
Roy, Sohini
Polavaram, Navatha S
Datta, Kaustubh
Bhola, Tanvi
Batra, Surinder K
Dutta, Samikshan
Band, Hamid
Hönscheid, Pia
AuthorAffiliation 1 Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
2 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
4 Eppley Cancer Institute, University of Nebraska Medical center, Omaha, Nebraska
6 Department of Urologic Research, Biochemistry, Mayo Clinic College of Medicine
3 Nebraska-Western Iowa Health Care System., Omaha VA Medical Center, Buffett Cancer Center
5 Institute of Pathology, Faculty of Medicine, Technische Universitaet, Dresden, Germany
AuthorAffiliation_xml – name: 2 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
– name: 4 Eppley Cancer Institute, University of Nebraska Medical center, Omaha, Nebraska
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Cites_doi 10.1186/1471-2407-9-220
10.15252/embr.201439637
10.1016/j.abb.2013.07.023
10.1006/excr.1994.1327
10.4161/auto.23783
10.1111/j.1600-0854.2008.00816.x
10.1016/j.tcb.2013.11.002
10.1016/j.ccr.2012.07.024
10.1016/j.ajpath.2013.05.020
10.1016/j.ccr.2008.01.029
10.1101/cshperspect.a016949
10.1074/jbc.M111.294470
10.1038/ncomms5904
10.1158/0008-5472.CAN-11-2656
10.1016/j.chembiol.2014.09.008
10.1158/2159-8290.CD-12-0085
10.1023/A:1026579711033
10.1111/febs.12770
10.1158/1078-0432.CCR-08-0563
10.1111/j.1600-0854.2008.00732.x
10.1096/fj.05-5646com
10.1038/nrc3627
10.1242/jcs.114.22.3991
10.1093/jnci/djm279
10.1158/0008-5472.CAN-09-0552
10.1038/cdd.2008.168
10.1093/carcin/bgl179
10.1158/0008-5472.CAN-12-0995
10.1016/j.biochi.2007.07.024
10.1158/0008-5472.CAN-11-3635
10.1186/1471-2121-15-15
10.3389/fonc.2015.00005
10.2741/3008
10.1038/nrc2521
10.1158/0008-5472.CAN-14-3380
10.1074/jbc.M804203200
10.4161/cc.25536
10.1002/emmm.201202078
10.3233/JAD-2011-101881
10.1016/j.devcel.2013.03.019
10.1186/1471-2121-8-3
10.1158/1078-0432.CCR-08-1520
10.1053/jpsu.2003.50091
10.1095/biolreprod.108.073312
10.1038/ncomms7240
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References Pelekanos (2022061705115953000_bib46) 2014; 15
Goel (2022061705115953000_bib12) 2013; 5
George (2022061705115953000_bib43) 2007; 8
Shisheva (2022061705115953000_bib30) 2013; 538
Tomas (2022061705115953000_bib35) 2014; 24
Muders (2022061705115953000_bib14) 2009; 69
Zhang (2022061705115953000_bib19) 2013; 12
Mellman (2022061705115953000_bib27) 2013; 5
Sharma (2022061705115953000_bib34) 2008; 9
Del Vecchio (2022061705115953000_bib40) 2012; 72
Stanton (2022061705115953000_bib17) 2013; 9
Ulmasov (2022061705115953000_bib23) 2013; 183
Fader (2022061705115953000_bib31) 2009; 16
Hu (2022061705115953000_bib24) 2015; 16
Bae (2022061705115953000_bib13) 2008; 283
Gray (2022061705115953000_bib16) 2008; 100
Bagri (2022061705115953000_bib1) 2009; 15
Pang (2022061705115953000_bib20) 2014; 5
Rush (2022061705115953000_bib36) 2012; 287
Goel (2022061705115953000_bib11) 2013; 13
Uniewicz (2022061705115953000_bib2) 2008; 13
Beierle (2022061705115953000_bib9) 2003; 38
Brix (2022061705115953000_bib32) 2008; 90
Capony (2022061705115953000_bib33) 1994; 215
Ridley (2022061705115953000_bib29) 2001; 114
Handa (2022061705115953000_bib10) 2000; 17
Karpanen (2022061705115953000_bib6) 2006; 20
Wang (2022061705115953000_bib22) 2015; 6
Lanahan (2022061705115953000_bib18) 2013; 25
Fritz (2022061705115953000_bib7) 2007; 28
Rizzolio (2022061705115953000_bib41) 2012; 72
Mosesson (2022061705115953000_bib28) 2008; 8
Ardito (2022061705115953000_bib44) 2012; 22
Lanzetti (2022061705115953000_bib45) 2008; 9
Dallas (2022061705115953000_bib3) 2008; 14
Caunt (2022061705115953000_bib4) 2008; 13
Yasuoka (2022061705115953000_bib5) 2009; 9
Miao (2022061705115953000_bib37) 2000; 19
Stanton (2022061705115953000_bib15) 2013; 73
Sferruzzi-Perri (2022061705115953000_bib26) 2009; 81
Arisi (2022061705115953000_bib25) 2011; 24
Chang (2022061705115953000_bib38) 2015; 75
Kohno (2022061705115953000_bib21) 2014; 21
Goel (2022061705115953000_bib8) 2012; 2
Padfield (2022061705115953000_bib39) 2015; 5
Shaughnessy (2022061705115953000_bib42) 2014; 281
References_xml – volume: 9
  start-page: 220
  year: 2009
  ident: 2022061705115953000_bib5
  article-title: Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression
  publication-title: BMC Cancer
  doi: 10.1186/1471-2407-9-220
  contributor:
    fullname: Yasuoka
– volume: 16
  start-page: 447
  year: 2015
  ident: 2022061705115953000_bib24
  article-title: WDFY1 mediates TLR3/4 signaling by recruiting TRIF
  publication-title: EMBO Rep
  doi: 10.15252/embr.201439637
  contributor:
    fullname: Hu
– volume: 538
  start-page: 171
  year: 2013
  ident: 2022061705115953000_bib30
  article-title: PtdIns5P: news and views of its appearance, disappearance and deeds
  publication-title: Arch Biochem Biophys
  doi: 10.1016/j.abb.2013.07.023
  contributor:
    fullname: Shisheva
– volume: 215
  start-page: 154
  year: 1994
  ident: 2022061705115953000_bib33
  article-title: Specific mannose-6-phosphate receptor-independent sorting of pro-cathepsin D in breast cancer cells
  publication-title: Exp Cell Res
  doi: 10.1006/excr.1994.1327
  contributor:
    fullname: Capony
– volume: 9
  start-page: 789
  year: 2013
  ident: 2022061705115953000_bib17
  article-title: Angiogenic growth factor axis in autophagy regulation
  publication-title: Autophagy
  doi: 10.4161/auto.23783
  contributor:
    fullname: Stanton
– volume: 9
  start-page: 2011
  year: 2008
  ident: 2022061705115953000_bib45
  article-title: Endocytosis and cancer: an ‘insider’ network with dangerous liaisons
  publication-title: Traffic
  doi: 10.1111/j.1600-0854.2008.00816.x
  contributor:
    fullname: Lanzetti
– volume: 24
  start-page: 26
  year: 2014
  ident: 2022061705115953000_bib35
  article-title: EGF receptor trafficking: consequences for signaling and cancer
  publication-title: Trends Cell Biol
  doi: 10.1016/j.tcb.2013.11.002
  contributor:
    fullname: Tomas
– volume: 22
  start-page: 304
  year: 2012
  ident: 2022061705115953000_bib44
  article-title: EGF receptor is required for KRAS-induced pancreatic tumorigenesis
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2012.07.024
  contributor:
    fullname: Ardito
– volume: 183
  start-page: 692
  year: 2013
  ident: 2022061705115953000_bib23
  article-title: Differences in the degree of cerulein-induced chronic pancreatitis in C57BL/6 mouse substrains lead to new insights in identification of potential risk factors in the development of chronic pancreatitis
  publication-title: Am J Pathol
  doi: 10.1016/j.ajpath.2013.05.020
  contributor:
    fullname: Ulmasov
– volume: 13
  start-page: 331
  year: 2008
  ident: 2022061705115953000_bib4
  article-title: Blocking neuropilin-2 function inhibits tumor cell metastasis
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2008.01.029
  contributor:
    fullname: Caunt
– volume: 5
  start-page: a016949
  year: 2013
  ident: 2022061705115953000_bib27
  article-title: Endocytosis and cancer
  publication-title: Cold Spring Harb Perspect Biol
  doi: 10.1101/cshperspect.a016949
  contributor:
    fullname: Mellman
– volume: 287
  start-page: 712
  year: 2012
  ident: 2022061705115953000_bib36
  article-title: Endosomal accumulation of the activated epidermal growth factor receptor (EGFR) induces apoptosis
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M111.294470
  contributor:
    fullname: Rush
– volume: 5
  start-page: 4904
  year: 2014
  ident: 2022061705115953000_bib20
  article-title: An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability
  publication-title: Nat Commun
  doi: 10.1038/ncomms5904
  contributor:
    fullname: Pang
– volume: 72
  start-page: 2657
  year: 2012
  ident: 2022061705115953000_bib40
  article-title: Epidermal growth factor receptor variant III contributes to cancer stem cell phenotypes in invasive breast carcinoma
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-11-2656
  contributor:
    fullname: Del Vecchio
– volume: 21
  start-page: 1522
  year: 2014
  ident: 2022061705115953000_bib21
  article-title: The membrane-lytic peptides K8L9 and melittin enter cancer cells via receptor endocytosis following subcytotoxic exposure
  publication-title: Chem Biol
  doi: 10.1016/j.chembiol.2014.09.008
  contributor:
    fullname: Kohno
– volume: 2
  start-page: 906
  year: 2012
  ident: 2022061705115953000_bib8
  article-title: VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer
  publication-title: Cancer Discov
  doi: 10.1158/2159-8290.CD-12-0085
  contributor:
    fullname: Goel
– volume: 19
  start-page: 29
  year: 2000
  ident: 2022061705115953000_bib37
  article-title: Neuropilin is a mediator of angiogenesis
  publication-title: Cancer Metastasis Rev
  doi: 10.1023/A:1026579711033
  contributor:
    fullname: Miao
– volume: 281
  start-page: 2172
  year: 2014
  ident: 2022061705115953000_bib42
  article-title: Epidermal growth factor receptor endocytic traffic perturbation by phosphatidate phosphohydrolase inhibition: new strategy against cancer
  publication-title: FEBS J
  doi: 10.1111/febs.12770
  contributor:
    fullname: Shaughnessy
– volume: 15
  start-page: 1860
  year: 2009
  ident: 2022061705115953000_bib1
  article-title: Neuropilins in tumor biology
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-08-0563
  contributor:
    fullname: Bagri
– volume: 9
  start-page: 995
  year: 2008
  ident: 2022061705115953000_bib34
  article-title: A role for EHD4 in the regulation of early endosomal transport
  publication-title: Traffic
  doi: 10.1111/j.1600-0854.2008.00732.x
  contributor:
    fullname: Sharma
– volume: 20
  start-page: 1462
  year: 2006
  ident: 2022061705115953000_bib6
  article-title: Functional interaction of VEGF-C and VEGF-D with neuropilin receptors
  publication-title: FASEB J
  doi: 10.1096/fj.05-5646com
  contributor:
    fullname: Karpanen
– volume: 13
  start-page: 871
  year: 2013
  ident: 2022061705115953000_bib11
  article-title: VEGF targets the tumour cell
  publication-title: Nat Rev Cancer
  doi: 10.1038/nrc3627
  contributor:
    fullname: Goel
– volume: 114
  start-page: 3991
  year: 2001
  ident: 2022061705115953000_bib29
  article-title: FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct functions in the endosomal and Golgi compartments
  publication-title: J Cell Sci
  doi: 10.1242/jcs.114.22.3991
  contributor:
    fullname: Ridley
– volume: 100
  start-page: 109
  year: 2008
  ident: 2022061705115953000_bib16
  article-title: Therapeutic targeting of neuropilin-2 on colorectal carcinoma cells implanted in the murine liver
  publication-title: J Natl Cancer Inst
  doi: 10.1093/jnci/djm279
  contributor:
    fullname: Gray
– volume: 69
  start-page: 6042
  year: 2009
  ident: 2022061705115953000_bib14
  article-title: Vascular endothelial growth factor-C protects prostate cancer cells from oxidative stress by the activation of mammalian target of rapamycin complex-2 and AKT-1
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-09-0552
  contributor:
    fullname: Muders
– volume: 16
  start-page: 70
  year: 2009
  ident: 2022061705115953000_bib31
  article-title: Autophagy and multivesicular bodies: two closely related partners
  publication-title: Cell Death Differ
  doi: 10.1038/cdd.2008.168
  contributor:
    fullname: Fader
– volume: 28
  start-page: 497
  year: 2007
  ident: 2022061705115953000_bib7
  article-title: The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice
  publication-title: Carcinogenesis
  doi: 10.1093/carcin/bgl179
  contributor:
    fullname: Fritz
– volume: 72
  start-page: 5801
  year: 2012
  ident: 2022061705115953000_bib41
  article-title: Neuropilin-1-dependent regulation of EGF-receptor signaling
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-12-0995
  contributor:
    fullname: Rizzolio
– volume: 17
  start-page: 291
  year: 2000
  ident: 2022061705115953000_bib10
  article-title: Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma
  publication-title: Int J Oncol
  contributor:
    fullname: Handa
– volume: 90
  start-page: 194
  year: 2008
  ident: 2022061705115953000_bib32
  article-title: Cysteine cathepsins: cellular roadmap to different functions
  publication-title: Biochimie
  doi: 10.1016/j.biochi.2007.07.024
  contributor:
    fullname: Brix
– volume: 73
  start-page: 160
  year: 2013
  ident: 2022061705115953000_bib15
  article-title: Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for treatment resistance
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-11-3635
  contributor:
    fullname: Stanton
– volume: 15
  start-page: 15
  year: 2014
  ident: 2022061705115953000_bib46
  article-title: Intracellular trafficking and endocytosis of CXCR4 in fetal mesenchymal stem/stromal cells
  publication-title: BMC Cell Biol
  doi: 10.1186/1471-2121-15-15
  contributor:
    fullname: Pelekanos
– volume: 5
  start-page: 5
  year: 2015
  ident: 2022061705115953000_bib39
  article-title: Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma
  publication-title: Front Oncol
  doi: 10.3389/fonc.2015.00005
  contributor:
    fullname: Padfield
– volume: 13
  start-page: 4339
  year: 2008
  ident: 2022061705115953000_bib2
  article-title: Neuropilins: a versatile partner of extracellular molecules that regulate development and disease
  publication-title: Front Biosci
  doi: 10.2741/3008
  contributor:
    fullname: Uniewicz
– volume: 8
  start-page: 835
  year: 2008
  ident: 2022061705115953000_bib28
  article-title: Derailed endocytosis: an emerging feature of cancer
  publication-title: Nat Rev Cancer
  doi: 10.1038/nrc2521
  contributor:
    fullname: Mosesson
– volume: 75
  start-page: 3077
  year: 2015
  ident: 2022061705115953000_bib38
  article-title: EGF receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-14-3380
  contributor:
    fullname: Chang
– volume: 283
  start-page: 28074
  year: 2008
  ident: 2022061705115953000_bib13
  article-title: Metabolic stress induces the lysosomal degradation of neuropilin-1 but not neuropilin-2
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M804203200
  contributor:
    fullname: Bae
– volume: 12
  start-page: 2163
  year: 2013
  ident: 2022061705115953000_bib19
  article-title: VEGFR2 trafficking: speed doesn't kill
  publication-title: Cell Cycle
  doi: 10.4161/cc.25536
  contributor:
    fullname: Zhang
– volume: 5
  start-page: 488
  year: 2013
  ident: 2022061705115953000_bib12
  article-title: GLI1 regulates a novel neuropilin-2/alpha6beta1 integrin based autocrine pathway that contributes to breast cancer initiation
  publication-title: EMBO Mol Med
  doi: 10.1002/emmm.201202078
  contributor:
    fullname: Goel
– volume: 24
  start-page: 721
  year: 2011
  ident: 2022061705115953000_bib25
  article-title: Gene expression biomarkers in the brain of a mouse model for Alzheimer's disease: mining of microarray data by logic classification and feature selection
  publication-title: J Alzheimers Dis
  doi: 10.3233/JAD-2011-101881
  contributor:
    fullname: Arisi
– volume: 25
  start-page: 156
  year: 2013
  ident: 2022061705115953000_bib18
  article-title: The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis
  publication-title: Dev Cell
  doi: 10.1016/j.devcel.2013.03.019
  contributor:
    fullname: Lanahan
– volume: 8
  start-page: 3
  year: 2007
  ident: 2022061705115953000_bib43
  article-title: Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and C. elegans
  publication-title: BMC Cell Biol
  doi: 10.1186/1471-2121-8-3
  contributor:
    fullname: George
– volume: 14
  start-page: 8052
  year: 2008
  ident: 2022061705115953000_bib3
  article-title: Neuropilin-2-mediated tumor growth and angiogenesis in pancreatic adenocarcinoma
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-08-1520
  contributor:
    fullname: Dallas
– volume: 38
  start-page: 514
  year: 2003
  ident: 2022061705115953000_bib9
  article-title: VEGF receptors are differentially expressed by neuroblastoma cells in culture
  publication-title: J Pediatr Surg
  doi: 10.1053/jpsu.2003.50091
  contributor:
    fullname: Beierle
– volume: 81
  start-page: 207
  year: 2009
  ident: 2022061705115953000_bib26
  article-title: Csf2 null mutation alters placental gene expression and trophoblast glycogen cell and giant cell abundance in mice
  publication-title: Biol Reprod
  doi: 10.1095/biolreprod.108.073312
  contributor:
    fullname: Sferruzzi-Perri
– volume: 6
  start-page: 6240
  year: 2015
  ident: 2022061705115953000_bib22
  article-title: Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells
  publication-title: Nat Commun
  doi: 10.1038/ncomms7240
  contributor:
    fullname: Wang
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Snippet Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many...
Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies where it has been implicated in promoting many...
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SubjectTerms Cell Line, Tumor
Endosomes - metabolism
ErbB Receptors - metabolism
Humans
Neoplasms - genetics
Neoplasms - pathology
Neuropilin-2 - genetics
Neuropilin-2 - metabolism
Title Neuropilin-2 Regulates Endosome Maturation and EGFR Trafficking to Support Cancer Cell Pathobiology
URI https://www.ncbi.nlm.nih.gov/pubmed/26560516
https://search.proquest.com/docview/1760877383
https://pubmed.ncbi.nlm.nih.gov/PMC4715955
Volume 76
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