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Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis.

Saddoughi SA, Gencer S, Peterson YK, Ward KE, Mukhopadhyay A, Oaks J, Bielawski J, Szulc ZM, Thomas RJ, Selvam SP, Senkal CE, Garrett-Mayer E, De Palma RM, Fedarovich D, Liu A, Habib AA, Stahelin RV, Perrotti D, Ogretmen B.

EMBO Mol Med. 2013 Jan;5(1):105-21. doi: 10.1002/emmm.201201283. Epub 2012 Nov 25.


Antagonistic activities of the immunomodulator and PP2A-activating drug FTY720 (Fingolimod, Gilenya) in Jak2-driven hematologic malignancies.

Oaks JJ, Santhanam R, Walker CJ, Roof S, Harb JG, Ferenchak G, Eisfeld AK, Van Brocklyn JR, Briesewitz R, Saddoughi SA, Nagata K, Bittman R, Caligiuri MA, Abdel-Wahab O, Levine R, Arlinghaus RB, Quintas-Cardama A, Goldman JM, Apperley J, Reid A, Milojkovic D, Ziolo MT, Marcucci G, Ogretmen B, Neviani P, Perrotti D.

Blood. 2013 Sep 12;122(11):1923-34. doi: 10.1182/blood-2013-03-492181. Epub 2013 Aug 7. Erratum in: Blood. 2014 May 8;123(19):3056.


FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma cells.

Zhang L, Wang H, Ding K, Xu J.

Toxicol Lett. 2015 Jul 2;236(1):43-59. doi: 10.1016/j.toxlet.2015.04.015. Epub 2015 May 1.


The therapeutic effects of SET/I2PP2A inhibitors on canine melanoma.

Enjoji S, Yabe R, Fujiwara N, Tsuji S, Vitek MP, Mizuno T, Nakagawa T, Usui T, Ohama T, Sato K.

J Vet Med Sci. 2015 Nov;77(11):1451-6. doi: 10.1292/jvms.15-0193. Epub 2015 Jun 11.


FTY720 induces apoptosis of M2 subtype acute myeloid leukemia cells by targeting sphingolipid metabolism and increasing endogenous ceramide levels.

Chen L, Luo LF, Lu J, Li L, Liu YF, Wang J, Liu H, Song H, Jiang H, Chen SJ, Luo C, Li KK.

PLoS One. 2014 Jul 22;9(7):e103033. doi: 10.1371/journal.pone.0103033. eCollection 2014.


Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor progression and poor prognosis in human non-small cell lung cancer.

Liu H, Gu Y, Wang H, Yin J, Zheng G, Zhang Z, Lu M, Wang C, He Z.

Oncotarget. 2015 Jun 20;6(17):14913-25.


PP2A inhibition is a common event in colorectal cancer and its restoration using FTY720 shows promising therapeutic potential.

Cristóbal I, Manso R, Rincón R, Caramés C, Senin C, Borrero A, Martínez-Useros J, Rodriguez M, Zazo S, Aguilera O, Madoz-Gúrpide J, Rojo F, García-Foncillas J.

Mol Cancer Ther. 2014 Apr;13(4):938-47. doi: 10.1158/1535-7163.MCT-13-0150. Epub 2014 Jan 21.


Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling.

Mukhopadhyay A, Saddoughi SA, Song P, Sultan I, Ponnusamy S, Senkal CE, Snook CF, Arnold HK, Sears RC, Hannun YA, Ogretmen B.

FASEB J. 2009 Mar;23(3):751-63. doi: 10.1096/fj.08-120550. Epub 2008 Nov 21.


Targeting inhibitor 2 of protein phosphatase 2A as a therapeutic strategy for prostate cancer treatment.

Mukhopadhyay A, Tabanor K, Chaguturu R, Aldrich JV.

Cancer Biol Ther. 2013 Oct 1;14(10):962-72. doi: 10.4161/cbt.25943. Epub 2013 Aug 5.


Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic cancer.

Farrell AS, Allen-Petersen B, Daniel CJ, Wang X, Wang Z, Rodriguez S, Impey S, Oddo J, Vitek MP, Lopez C, Christensen DJ, Sheppard B, Sears RC.

Mol Cancer Res. 2014 Jun;12(6):924-39. doi: 10.1158/1541-7786.MCR-13-0542. Epub 2014 Mar 25.


Effect of FTY720 on the SET-PP2A complex in acute myeloid leukemia; SET binding drugs have antagonistic activity.

Pippa R, Dominguez A, Christensen DJ, Moreno-Miralles I, Blanco-Prieto MJ, Vitek MP, Odero MD.

Leukemia. 2014 Sep;28(9):1915-8. doi: 10.1038/leu.2014.141. Epub 2014 Apr 30. No abstract available.


Lyn sustains oncogenic signaling in chronic lymphocytic leukemia by strengthening SET-mediated inhibition of PP2A.

Zonta F, Pagano MA, Trentin L, Tibaldi E, Frezzato F, Trimarco V, Facco M, Zagotto G, Pavan V, Ribaudo G, Bordin L, Semenzato G, Brunati AM.

Blood. 2015 Jun 11;125(24):3747-55. doi: 10.1182/blood-2014-12-619155. Epub 2015 Apr 30.


Ceramide in the prostate.

Dent P.

Cancer Biol Ther. 2013 Oct 1;14(10):881-2. doi: 10.4161/cbt.26212. Epub 2013 Aug 19.


SET antagonist enhances the chemosensitivity of non-small cell lung cancer cells by reactivating protein phosphatase 2A.

Hung MH, Wang CY, Chen YL, Chu PY, Hsiao YJ, Tai WT, Chao TT, Yu HC, Shiau CW, Chen KF.

Oncotarget. 2016 Jan 5;7(1):638-55. doi: 10.18632/oncotarget.6313.


Receptor-interacting Ser/Thr kinase 1 (RIPK1) and myosin IIA-dependent ceramidosomes form membrane pores that mediate blebbing and necroptosis.

Nganga R, Oleinik N, Kim J, Selvam SP, De Palma R, Johnson KA, Parikh RY, Gangaraju V, Peterson Y, Dany M, Stahelin RV, Voelkel-Johnson C, Szulc ZM, Bieberich E, Ogretmen B.

J Biol Chem. 2019 Jan 11;294(2):502-519. doi: 10.1074/jbc.RA118.005865. Epub 2018 Nov 12.


RIPK1 can function as an inhibitor rather than an initiator of RIPK3-dependent necroptosis.

Kearney CJ, Cullen SP, Clancy D, Martin SJ.

FEBS J. 2014 Nov;281(21):4921-34. doi: 10.1111/febs.13034. Epub 2014 Oct 4.


Fingolimod targeting protein phosphatase 2A differently affects IL-33 induced IL-2 and IFN-γ production in CD8(+) lymphocytes.

Ottenlinger F, Schwiebs A, Pfarr K, Wagner A, Grüner S, Mayer CA, Pfeilschifter JM, Radeke HH.

Eur J Immunol. 2016 Apr;46(4):941-51. doi: 10.1002/eji.201545805. Epub 2016 Jan 13.


Antitumor effects of OSU-2S, a nonimmunosuppressive analogue of FTY720, in hepatocellular carcinoma.

Omar HA, Chou CC, Berman-Booty LD, Ma Y, Hung JH, Wang D, Kogure T, Patel T, Terracciano L, Muthusamy N, Byrd JC, Kulp SK, Chen CS.

Hepatology. 2011 Jun;53(6):1943-58. doi: 10.1002/hep.24293. Epub 2011 May 2.


Isoliensinine induces dephosphorylation of NF-kB p65 subunit at Ser536 via a PP2A-dependent mechanism in hepatocellular carcinoma cells: roles of impairing PP2A/I2PP2A interaction.

Shu G, Zhang L, Jiang S, Cheng Z, Wang G, Huang X, Yang X.

Oncotarget. 2016 Jun 28;7(26):40285-40296. doi: 10.18632/oncotarget.9603.

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