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Dong et al. UPI peptide as cancer therapeutic

and CRISPR/Cas9 (clustered regularly interspaced Semin Oncol 2009;36:S12-9.
short palindromic repeats/CRISPR associated protein 4. Blázquez C, Casanova ML, Planas A, Gómez Del Pulgar T, Villanueva
9) genome editing [37-39] may also provide new directions C, Fernández-Aceñero MJ, Aragonés J, Huffman JW, Jorcano JL,
to develop novel therapeutic agents. Guzmán M. Inhibition of tumor angiogenesis by cannabinoids.
FASEB J 2003;17:529-31.
5. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature
CONCLUSION 2005;438:967-74.
6. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003;9:653-
The UPI peptide is a promising compound to treat 60.
cancers. The UPI peptide can efficiently inhibit 7. Adams RH, Alitalo K. Molecular regulation of angiogenesis and
tumor growth and metastasis and specifically targets lymphangiogenesis. Nat Rev Mol Cell Biol 2007;8:464-78.
VEGFR2 signaling to create upregulated, nonfunctional 8. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications
of angiogenesis. Nature 2011;473:298-307.
tumor vessels. It is expected that the peptide may be 9. Jain RK, Duda DG, Clark JW, Loeffler JS. Lessons from phase III
applicable to treat cancer patients as a first or second clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol
line compound; or as an alternative replacement to the 2006;3:24-40.
anti-VEGF antibody in patients who are resistant to 10. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases.
anti-angiogenic therapies. Nature 2000;407:249-57.
11. Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P,
Acknowledgments Gale NW, Lin HC, Yancopoulos GD, Thurston G. Blockade of Dll4
inhibits tumour growth by promoting non-productive angiogenesis.
We thank Dr. Pierre Tuffery in the Institut National de la Nature 2006;444:1032-7.
Santé et de la Recherche Médicale (INSERM) for his 12. Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y,
help in performing the molecular modeling of D- and Kowalski J, Watts RJ, Callahan C, Kasman I, Singh M, Chien M,
L-amino acids for UIM or UPI peptide docking. Scott Tan C, Hongo JA, de Sauvage F, Plowman G, Yan M. Inhibition of
Wong helped us to edit the manuscript. Dll4 signalling inhibits tumour growth by deregulating angiogenesis.
Nature 2006;444:1083-7.
13. Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten
Financial support and sponsorship G, Eliceiri BP, Reisfeld RA. A DNA vaccine against VEGF receptor
This work was supported in part by National Institutes 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med
of Health (NIH) grants R01HL-093242, R01 HL118676, 2002;8:1369-75.
R01HL-130845, P20 RR018758; an AHA Established 14. Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore
PP, De Camilli P. Epsin is an EH-domain-binding protein implicated
Investigator Award; a National Scientific Development in clathrin-mediated endocytosis. Nature 1998;394:793-7.
Grant from the American Heart Association 15. Tessneer KL, Cai X, Pasula S, Dong Y, Liu X, Chang B, McManus
(0835544N); and a grant from the Department of J, Hahn S, Yu L, Chen H. Epsin family of endocytic adaptor proteins
Defense W81XWH-11-1-00226 to author HC; by as oncogenic regulators of cancer progression. J Can Res Updates
OCAST grants AR11-043, HR14-056; and American 2013;2:144-50.
Heart Association AHA-SDG grant 12SDG8760002 16. Chen H, Ko G, Zatti A, Di Giacomo G, Liu L, Raiteri E, Perucco E,
to author YD. Author JD is a recipient of the Fleming Collesi C, Min W, Zeiss C, De Camilli P, Cremona O. Embryonic
arrest at midgestation and disruption of Notch signaling produced by
Scholar Award from the Oklahoma Medical Research the absence of both epsin 1 and epsin 2 in mice. Proc Natl Acad Sci U
Foundation. S A 2009;106:13838-43.
17. Rahman HN, Wu H, Dong Y, Pasula S, Wen A, Sun Y, Brophy ML,
Conflicts of interest Tessneer KL, Cai X, McManus J, Chang B, Kwak S, Rahman NS, Xu
There are no conflicts of interest. W, Fernandes C, McDaniel JM, Xia L, Smith L, Srinivasan RS, Chen
H. Selective targeting of a novel epsin-VEGFR2 interaction promotes
VEGF-mediated angiogenesis. Circ Res 2016;118:957-69.
Patient consent 18. Liu X, Pasula S, Song H, Tessneer KL, Dong Y, Hahn S, Yago T,
Not applicable. Brophy ML, Chang B, Cai X, Wu H, McManus J, Ichise H, Georgescu
C, Wren JD, Griffin C, Xia L, Srinivasan RS, Chen H. Temporal
Ethics approval and spatial regulation of epsin abundance and VEGFR3 signaling
Not applicable. are required for lymphatic valve formation and function. Sci Signal
2014;7:ra97.
19. Dong Y, Wu H, Rahman HN, Liu Y, Pasula S, Tessneer KL, Cai
REFERENCES X, Liu X, Chang B, McManus J, Hahn S, Dong J, Brophy ML, Yu
L, Song K, Silasi-Mansat R, Saunders D, Njoku C, Song H, Mehta-
1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J D’Souza P, Towner R, Lupu F, McEver RP, Xia L, Boerboom D,
Med 1971;285:1182-6. Srinivasan RS, Chen H. Motif mimetic of epsin perturbs tumor growth
2. Cao Y, Langer R. A review of Judah Folkman’s remarkable and metastasis. J Clin Invest 2015;125:4349-64.
achievements in biomedicine. Proc Natl Acad Sci U S A 20. Pasula S, Cai X, Dong Y, Messa M, McManus J, Chang B, Liu X,
2008;105:13203-5. Zhu H, Mansat RS, Yoon SJ, Hahn S, Keeling J, Saunders D, Ko
3. Gaur P, Bose D, Samuel S, Ellis LM. Targeting tumor angiogenesis. G, Knight J, Newton G, Luscinskas F, Sun X, Towner R, Lupu F,
10 Vessel Plus ¦ Volume 1 ¦ March 31, 2017