Artículo

Ramakrishnan, S.; Granger, V.; Rak, M.; Hu, Q.; Attwood, K.; Aquila, L.; Krishnan, N.; Osiecki, R.; Azabdaftari, G.; Guru, K.; Chatta, G.; Gueron, G.; McNally, L.; Ohm, J.; Wang, J.; Woloszynska, A. "Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer" (2019) Cell Death and Differentiation
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Abstract:

Lysine-specific demethylase 6A (KDM6A) and members of the Switch/Sucrose Non-Fermentable (SWI/SNF) family are known to counteract the activity of Enhancer of Zeste Homolog 2 (EZH2), which is often overexpressed and is associated with poor prognosis in muscle-invasive bladder cancer. Here we provide evidence that alterations in chromatin modifying enzymes, including KDM6A and members of the SWI/SNF complex, are frequent in muscle-invasive bladder cancer. We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. We reveal a novel mechanism of action of EZH2 inhibition, alone and in combination with cisplatin, which induces immune signaling with the largest changes observed in interferon gamma (IFN-γ). This upregulation is a result of activated natural killer (NK) signaling as demonstrated by the increase in NK cell-associated genes MIP-1α, ICAM1, ICAM2, and CD86 in xenografts treated with EZH2 inhibitors. Conversely, EZH2 inhibition results in decreased expression of pluripotency markers, ALDH2 and CK5, and increased cell death. Our results reveal a novel sensitivity of muscle-invasive bladder cancer cells with KMD6A and SWI/SNF mutations to EZH2 inhibition alone and in combination with cisplatin. This sensitivity is mediated through increased NK cell-related signaling resulting in tumor cell differentiation and cell death. © 2019, ADMC Associazione Differenziamento e Morte Cellulare.

Registro:

Documento: Artículo
Título:Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer
Autor:Ramakrishnan, S.; Granger, V.; Rak, M.; Hu, Q.; Attwood, K.; Aquila, L.; Krishnan, N.; Osiecki, R.; Azabdaftari, G.; Guru, K.; Chatta, G.; Gueron, G.; McNally, L.; Ohm, J.; Wang, J.; Woloszynska, A.
Filiación:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
Department of Cell Biology, Jagiellonian University, Krakow, 31-007, Poland
Department of Bioinformatics and BioStatistics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
Child Jesus Hospital, Warsaw, 02-005, Poland
Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
Department of Medicine-GU Center, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
Department of Biological Chemistry, University of Buenos Aires, IQUIBICEN-CONICET, Intendente Guiraldes 2160, CABA, Buenos Aires, 1428, Argentina
Department of Cancer Biology, Wake Forest Comprehensive Cancer Center, Winston-Salem, NC 27157, United States
Department of Cancer Genetics and Genomics, Comprehensive Cancer Center, Buffalo, NY 14263, United States
Año:2019
DOI: http://dx.doi.org/10.1038/s41418-019-0278-9
Título revista:Cell Death and Differentiation
Título revista abreviado:Cell Death Differ.
ISSN:13509047
CODEN:CDDIE
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13509047_v_n_p_Ramakrishnan

Referencias:

  • Nargund, A.M., Pham, C.G., Dong, Y., Wang, P.I., Osmangeyoglu, H.U., Xie, Y., The SWI/SNF protein PBRM1 restrains VHL-loss-driven clear cell renal cell carcinoma (2017) Cell Rep, 18, pp. 2893-2906. , COI: 1:CAS:528:DC%2BC2sXkvFWrsr0%3D
  • Mathur, R., Alver, B.H., San Roman, A.K., Wilson, B.G., Wang, X., Agoston, A.T., ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice (2017) Nat Genet, 49, pp. 296-302. , COI: 1:CAS:528:DC%2BC28XitFWnsbfP
  • Aldiri, I., Ajioka, I., Xu, B., Zhang, J., Chen, X., Benavente, C., Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma (2015) Development, 142, pp. 4092-4106. , COI: 1:CAS:528:DC%2BC28XntFSmsbs%3D
  • Gao, S.B., Zheng, Q.F., Xu, B., Pan, C.B., Li, K.L., Zhao, Y., EZH2 represses target genes through H3K27-dependent and H3K27-independent mechanisms in hepatocellular carcinoma (2014) Mol Cancer Res, 12, pp. 1388-1397. , COI: 1:CAS:528:DC%2BC2cXhslKns73O
  • Venkatesan, N., Wong, J.F., Tan, K.P., Chung, H.H., Yau, Y.H., Cukuroglu, E., EZH2 promotes neoplastic transformation through VAV interaction-dependent extranuclear mechanisms (2018) Oncogene, 37, pp. 461-477. , COI: 1:CAS:528:DC%2BC2sXhsFygu7%2FK
  • Beguelin, W., Teater, M., Gearhart, M.D., Calvo Fernandez, M.T., Goldstein, R.L., Cardenas, M.G., EZH2 and BCL6 cooperate to assemble CBX8-BCOR complex to repress bivalent promoters, mediate germinal center formation and lymphomagenesis (2016) Cancer Cell, 30, pp. 197-213. , COI: 1:CAS:528:DC%2BC28XhtlCrtLnL
  • Wilson, B.G., Wang, X., Shen, X., McKenna, E.S., Lemieux, M.E., Cho, Y.J., Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation (2010) Cancer Cell, 18, pp. 316-328. , COI: 1:CAS:528:DC%2BC3cXhtlSnu77J
  • Kia, S.K., Gorski, M.M., Giannakopoulos, S., Verrijzer, C.P., SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus (2008) Mol Cell Biol, 28, pp. 3457-3464. , COI: 1:CAS:528:DC%2BD1cXlvFeqs7g%3D
  • Karakashev, S., Zhu, H., Wu, S., Yokoyama, Y., Bitler, B.G., Park, P.H., CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity (2018) Nat Commun, 9
  • Januario, T., Ye, X., Bainer, R., Alicke, B., Smith, T., Haley, B., PRC2-mediated repression of SMARCA2 predicts EZH2 inhibitor activity in SWI/SNF mutant tumors (2017) Proc Natl Acad Sci USA, 114, pp. 12249-12254. , COI: 1:CAS:528:DC%2BC2sXhslemsr3K
  • Knutson, S.K., Warholic, N.M., Wigle, T.J., Klaus, C.R., Allain, C.J., Raimondi, A., Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2 (2013) PNAS, 110, pp. 7922-7927. , COI: 1:CAS:528:DC%2BC3sXptFGrurw%3D
  • Bitler, B.G., Aird, K.M., Zhang, R., Epigenetic synthetic lethality in ovarian clear cell carcinoma: EZH2 and ARID1A mutations (2016) Mol Cell Oncol, 3
  • Kim, K.H., Kim, W., Howard, T.P., Vazquez, F., Tsherniak, A., Wu, J.N., SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2 (2015) Nat Med, 21, p. 1491. , COI: 1:CAS:528:DC%2BC2MXhslKgt7nK
  • Chan-Penebre, E., Armstrong, K., Drew, A., Grassian, A.R., Feldman, I., Knutson, S.K., Selective killing of SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type cells by inhibition of EZH2: in vitro and in vivo preclinical models (2017) Mol Cancer Ther, 16, pp. 850-860. , COI: 1:CAS:528:DC%2BC2sXmvFemt74%3D
  • Morel, D., Almouzni, G., Soria, J.C., Postel-Vinay, S., Targeting chromatin defects in selected solid tumors based on oncogene addiction, synthetic lethality and epigenetic antagonism (2017) Ann Oncol, 28, pp. 254-269. , COI: 1:STN:280:DC%2BC1cvpsVOqtw%3D%3D, PID: 28426098
  • Liu, L., Xu, Z., Zhong, L., Wang, H., Jiang, S., Long, Q., Enhancer of zeste homolog 2 (EZH2) promotes tumour cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma (2016) BJU Int, 117, pp. 351-362. , COI: 1:CAS:528:DC%2BC28XpsFansg%3D%3D
  • Lv, Y.F., Yan, G.N., Meng, G., Zhang, X., Guo, Q.N., Enhancer of zeste homolog 2 silencing inhibits tumor growth and lung metastasis in osteosarcoma (2015) Sci Rep, 5. , COI: 1:CAS:528:DC%2BC2MXhsVKhs7vJ
  • Pawlyn, C., Bright, M.D., Buros, A.F., Stein, C.K., Walters, Z., Aronson, L.I., Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control (2017) Blood Cancer J, 7. , COI: 1:STN:280:DC%2BC1cvjtFeisA%3D%3D
  • Agger, K., Cloos, P.A.C., Christensen, J., Pasini, D., Rose, S., Rappsilber, J., UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development (2007) Nature, 449, pp. 731-734. , COI: 1:CAS:528:DC%2BD2sXhtFChu77P
  • Shpargel, K.B., Starmer, J., Wang, C., Ge, K., Magnuson, T., UTX-guided neural crest function underlies craniofacial features of Kabuki syndrome (2017) PNAS, 114, pp. E9046-E9055. , COI: 1:CAS:528:DC%2BC2sXhs1aju7nK
  • Hong, S., Cho, Y.W., Yu, L.R., Yu, H., Veenstra, T.D., Ge, K., Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases (2007) PNAS, 104, pp. 18439-18444. , COI: 1:CAS:528:DC%2BD2sXhtl2ku7rI
  • Ler, L.D., Ghosh, S., Chai, X., Thike, A.A., Heng, H.L., Siew, E.Y., Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2 (2017) Sci Transl Med, 9. , eaai8312
  • Gui, Y., Guo, G., Huang, Y., Hu, X., Tang, A., Gao, S., Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder (2011) Nat Genet, 43, p. 875. , COI: 1:CAS:528:DC%2BC3MXpvVOmurg%3D
  • Comprehensive molecular characterization of urothelial bladder carcinoma (2014) Nature, 507, pp. 315-322
  • Lee, S.R., Roh, Y.G., Kim, S.K., Lee, J.S., Seol, S.Y., Lee, H.H., Activation of EZH2 and SUZ12 regulated by E2F1 predicts the disease progression and aggressive characteristics of bladder cancer (2015) Clin Cancer Res, 21, pp. 5391-5403. , COI: 1:CAS:528:DC%2BC2MXhvFKlurrN
  • Warrick, J.I., Raman, J.D., Kaag, M., Bruggeman, T., Cates, J., Clark, P., Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer (2016) Urol Oncol, 34, pp. 258.e251-256
  • Tuominen, V.J., Ruotoistenmaki, S., Viitanen, A., Jumppanen, M., Isola, J., ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 (2010) Breast Cancer Res, 12
  • https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm559300.htm; Powles, T., O’Donnell, P.H., Massard, C., Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study (2017) JAMA Oncol, 3
  • Sonpavde, G., Sternberg, C.N., Rosenberg, J.E., Hahn, N.M., Galsky, M.D., Vogelzang, N.J., Second-line systemic therapy and emerging drugs for metastatic transitional-cell carcinoma of the urothelium (2010) Lancet Oncol, 11, pp. 861-870. , COI: 1:CAS:528:DC%2BC3cXhtFWqsrzN
  • Wilson, B.G., Roberts, C.W.M., SWI/SNF nucleosome remodellers and cancer (2011) Nat Rev Cancer, 11, p. 481. , COI: 1:CAS:528:DC%2BC3MXntFKrsLw%3D
  • Bracken, A.P., Dietrich, N., Pasini, D., Hansen, K.H., Helin, K., Genome-wide mapping of polycomb target genes unravels their roles in cell fate transitions (2006) Genes Dev, 20, pp. 1123-1136. , COI: 1:CAS:528:DC%2BD28XkslCjsbs%3D
  • Bitler, B.G., Aird, K.M., Garipov, A., Li, H., Amatangelo, M., Kossenkov, A.V., Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers (2015) Nat Med, 21, p. 231. , COI: 1:CAS:528:DC%2BC2MXivVSit7k%3D
  • Forbes, S.A., Beare, D., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., COSMIC: exploring the world’s knowledge of somatic mutations in human cancer (2015) Nucleic Acids Res, 43 (Database issue), pp. D805-D811. , COI: 1:CAS:528:DC%2BC2sXhtV2itr3F
  • Bowman, K.J., Al-Moneef, M.M., Sherwood, B.T., Colquhoun, A.J., Goddard, J.C., Griffiths, T.R., Comet assay measures of DNA damage are predictive of bladder cancer cell treatment sensitivity in vitro and outcome in vivo (2014) Int J Cancer, 134, pp. 1102-1111. , COI: 1:CAS:528:DC%2BC3sXhsFOgu73J
  • Ferreira-Teixeira, M., Paiva-Oliveira, D., Parada, B., Alves, V., Sousa, V., Chijioke, O., Natural killer cell-based adoptive immunotherapy eradicates and drives differentiation of chemoresistant bladder cancer stem-like cells (2016) BMC Med, 14
  • Li, L., Li, W., Wang, C., Yan, X., Wang, Y., Niu, C., Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma (2018) Cytotherapy, 20, pp. 134-148. , COI: 1:CAS:528:DC%2BC2sXhs1yrt7jJ
  • Jin, X., Kim, L.J.Y., Wu, Q., Wallace, L.C., Prager, B.C., Sanvoranart, T., Targeting glioma stem cells through combined BMI1 and EZH2 inhibition (2017) Nat Med, 23, pp. 1352-1361. , COI: 1:CAS:528:DC%2BC2sXhs1aisrzJ, PID: 29035367
  • Liu, H., Sun, Q., Sun, Y., Zhang, J., Yuan, H., Pang, S., MELK and EZH2 cooperate to regulate medulloblastoma cancer stem-like cell proliferation and differentiation (2017) Mol Cancer Res, 15, pp. 1275-1286
  • Rizzo, S., Hersey, J.M., Mellor, P., Dai, W., Santos-Silva, A., Liber, D., Ovarian cancer stem cell like side populations are enriched following chemotherapy and overexpress EZH2 (2011) Mol Cancer Ther, 10, pp. 325-335. , COI: 1:CAS:528:DC%2BC3MXhs1ylsLg%3D
  • Wang, L., Liu, X., Ren, Y., Zhang, J., Chen, J., Zhou, W., Cisplatin-enriching cancer stem cells confer multidrug resistance in non-small cell lung cancer via enhancing TRIB1/HDAC activity (2017) Cell Death Dis, 8. , COI: 1:CAS:528:DC%2BC2sXmtVCrs7w%3D
  • Kozlowska, A.K., Topchyan, P., Kaur, K., Tseng, H.C., Teruel, A., Hiraga, T., Differentiation by NK cells is a prerequisite for effective targeting of cancer stem cells/poorly differentiated tumors by chemopreventive and chemotherapeutic drugs (2017) J Cancer, 8, pp. 537-554. , COI: 1:CAS:528:DC%2BC1cXhtl2msbbP
  • Van Batavia, J., Yamany, T., Molotkov, A., Dan, H., Mansukhani, M., Batourina, E., Bladder cancers arise from distinct urothelial sub-populations (2014) Nat Cell Biol, 16, pp. 982-991. , 981-5
  • Chen, Y., Zhou, B., Chen, D., USP21 promotes cell proliferation and metastasis through suppressing EZH2 ubiquitination in bladder carcinoma (2017) Onco Targets Ther, 10, pp. 681-689. , COI: 1:CAS:528:DC%2BC1cXhsFeltLnL
  • Karantanos, T., Boussiotis, V.A., JAK3-mediated phosphorylation of EZH2: a novel mechanism of non-canonical EZH2 activation and oncogenic function (2016) Transl Cancer Res, 5, pp. S1208-s1211
  • Yan, J., Li, B., Lin, B., Lee, P.T., Chung, T.H., Tan, J., EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma (2016) Blood, 128, pp. 948-958. , COI: 1:CAS:528:DC%2BC28XhslOkt73E
  • Santos, M., Martinez-Fernandez, M., Duenas, M., Garcia-Escudero, R., Alfaya, B., Villacampa, F., In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer (2014) Cancer Res, 74, pp. 6565-6577. , COI: 1:CAS:528:DC%2BC2cXhvFWks77N
  • Wee, Z.N., Li, Z., Lee, P.L., Lee, S.T., Lim, Y.P., Yu, Q., EZH2-mediated inactivation of IFN-gamma-JAK-STAT1 signaling is an effective therapeutic target in MYC-driven prostate cancer (2014) Cell Rep, 8, pp. 204-216. , COI: 1:CAS:528:DC%2BC2cXhtVCjurzJ
  • Böttcher, J.P., Bonavita, E., Chakravarty, P., Blees, H., Cabeza-Cabrerizo, M., Sammicheli, S., NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control (2018) Cell, 172, pp. 1022-1037.e1014
  • Noman, M.Z., Berchem, G., Janji, B., Targeting autophagy blocks melanoma growth by bringing natural killer cells to the tumor battlefield (2018) Autophagy, 14, pp. 730-732
  • Guerra, N., Tan, Y.X., Joncker, N.T., Choy, A., Gallardo, F., Xiong, N., NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy (2008) Immunity, 28, pp. 571-580. , COI: 1:CAS:528:DC%2BD1cXkvV2itL8%3D
  • Bugide, S., Green, M.R., Wajapeyee, N., Inhibition of Enhancer of zeste homolog 2 (EZH2) induces natural killer cell-mediated eradication of hepatocellular carcinoma cells (2018) Proc Natl Acad Sci USA, 115, pp. E3509-E3518
  • Cribbs, A., Hookway, E.S., Wells, G., Lindow, M., Obad, S., Oerum, H., Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells (2018) J Biol Chem, 293, pp. 2422-2437. , COI: 1:CAS:528:DC%2BC1cXivVCktr0%3D
  • Yin, J., Leavenworth, J.W., Li, Y., Luo, Q., Xie, H., Liu, X., Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity (2015) PNAS, 112, pp. 15988-15993. , COI: 1:CAS:528:DC%2BC2MXitVWjtLvM
  • Ikeda, H., Old, L.J., Schreiber, R.D., The roles of IFN gamma in protection against tumor development and cancer immunoediting (2002) Cytokine Growth Factor Rev, 13, pp. 95-109. , COI: 1:CAS:528:DC%2BD38XitFWhsrs%3D
  • Cany, J., Roeven, M.W.H., Hoogstad-van Evert, J.S., Hobo, W., Maas, F., Franco Fernandez, R., Decitabine enhances targeting of AML cells by CD34(+) progenitor-derived NK cells in NOD/SCID/IL2Rg(null) mice (2018) Blood, 131, pp. 202-214. , COI: 1:CAS:528:DC%2BC1cXhs1Cqsr7J
  • Baragano Raneros, A., Martin-Palanco, V., Fernandez, A.F., Rodriguez, R.M., Fraga, M.F., Lopez-Larrea, C., Methylation of NKG2D ligands contributes to immune system evasion in acute myeloid leukemia (2015) Genes Immun, 16, pp. 71-82. , COI: 1:CAS:528:DC%2BC2cXhvFCiur7O
  • Zingg, D., Arenas-Ramirez, N., Sahin, D., Rosalia, R.A., Antunes, A.T., Haeusel, J., The histone methyltransferase Ezh2 controls mechanisms of adaptive resistance to tumor immunotherapy (2017) Cell Rep, 20, pp. 854-867. , COI: 1:CAS:528:DC%2BC2sXht1Gis7fP
  • Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy (2015) Nature, 527, pp. 249-253. , COI: 1:CAS:528:DC%2BC2MXhslOrtLjI
  • Tang, S.H., Huang, H.S., Wu, H.U., Tsai, Y.T., Chuang, M.J., Yu, C.P., Pharmacologic down-regulation of EZH2 suppresses bladder cancer in vitro and in vivo (2014) Oncotarget, 5, pp. 10342-10355. , PID: 25431950
  • Kim, S.H., Joshi, K., Ezhilarasan, R., Myers, T.R., Siu, J., Gu, C., EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner (2015) Stem Cell Rep, 4, pp. 226-238. , COI: 1:CAS:528:DC%2BC2MXhtVGms7o%3D
  • Chen, J.F., Luo, X., Xiang, L.S., Li, H.T., Zha, L., Li, N., EZH2 promotes colorectal cancer stem-like cell expansion by activating p21cip1-Wnt/beta-catenin signaling (2016) Oncotarget, 7, pp. 41540-41558. , PID: 27172794
  • Chan, K.S., Molecular pathways: targeting cancer stem cells awakened by chemotherapy to abrogate tumor repopulation (2016) Clin Cancer Res, 22, pp. 802-806. , COI: 1:CAS:528:DC%2BC28XivFGmsbg%3D
  • Chen, Z., Zhu, P., Zhang, Y., Liu, Y., He, Y., Zhang, L., Enhanced sensitivity of cancer stem cells to chemotherapy using functionalized mesoporous silica nanoparticles (2016) Mol Pharm, 13, pp. 2749-2759. , COI: 1:CAS:528:DC%2BC28XhtVGjtLrP

Citas:

---------- APA ----------
Ramakrishnan, S., Granger, V., Rak, M., Hu, Q., Attwood, K., Aquila, L., Krishnan, N.,..., Woloszynska, A. (2019) . Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer. Cell Death and Differentiation.
http://dx.doi.org/10.1038/s41418-019-0278-9
---------- CHICAGO ----------
Ramakrishnan, S., Granger, V., Rak, M., Hu, Q., Attwood, K., Aquila, L., et al. "Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer" . Cell Death and Differentiation (2019).
http://dx.doi.org/10.1038/s41418-019-0278-9
---------- MLA ----------
Ramakrishnan, S., Granger, V., Rak, M., Hu, Q., Attwood, K., Aquila, L., et al. "Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer" . Cell Death and Differentiation, 2019.
http://dx.doi.org/10.1038/s41418-019-0278-9
---------- VANCOUVER ----------
Ramakrishnan, S., Granger, V., Rak, M., Hu, Q., Attwood, K., Aquila, L., et al. Inhibition of EZH2 induces NK cell-mediated differentiation and death in muscle-invasive bladder cancer. Cell Death Differ. 2019.
http://dx.doi.org/10.1038/s41418-019-0278-9