A functional siRNA screen identifies genes modulating angiotensin II-mediated EGFR transactivation

Journal of Cell Science

Volumn 126, Issue 23, 2013, Pages 5377-5390

  George, Amee ^a,b,c,d   Purdue, Brooke W ^a   Gould, Cathryn M ^c   Thomas, Daniel W ^c   Handoko, Yanny ^c   Qian, Hongwei ^e   Quaife Ryan, Gregory A ^a   Morgan, Kylie A ^b   Simpson, Kaylene J ^c,d   Thomas, Walter G ^a   Hannan, Ross D ^a,b,c,d,f  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b PETER MACCALLUM CANCER CENTRE   (Australia)

^c Peter MacCallum Cancer   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^f MONASH UNIVERSITY   (Australia)

Author keywords

Angiotensin; EGFR; G protein coupled receptor; SiRNA; Transactivation

Indexed keywords

ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN II; EPIDERMAL GROWTH FACTOR RECEPTOR; G PROTEIN COUPLED RECEPTOR; SMALL INTERFERING RNA;

ARTICLE; BREAST EPITHELIUM; CELL STIMULATION; GENETIC SCREENING; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; TRANSACTIVATION;

ANGIOTENSIN; EGFR; G PROTEIN-COUPLED RECEPTOR; SIRNA, TRANSACTIVATION;

ANGIOTENSIN II; CELL LINE, TRANSFORMED; CHOLINE KINASE; EPIDERMAL GROWTH FACTOR; EPITHELIAL CELLS; FEMALE; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HUMANS; MAMMARY GLANDS, HUMAN; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; RECEPTOR, ANGIOTENSIN, TYPE 1; RECEPTOR, EPIDERMAL GROWTH FACTOR; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; THROMBIN; TRANSCRIPTIONAL ACTIVATION;

EID: 84890217761     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.128280     Document Type: Article

References (78)

1. Abramoff, M. D., Magalhaes, P. J. and Ram, S. J. (2004). Image Processing with ImageJ. Biophotonics Intern. 11, 36-42.
2. Andreev, J., Galisteo, M. L., Kranenburg, O., Logan, S. K., Chiu, E. S., Okigaki, M., Cary, L. A., Moolenaar, W. H. and Schlessinger, J. (2001). Src and Pyk2 mediate G-protein-coupled receptor activation of epidermal growth factor receptor (EGFR) but are not required for coupling to the mitogen-activated protein (MAP) kinase signaling cascade. J. Biol. Chem. 276, 20130-20135.
3. Aoyama, C., Liao, H. and Ishidate, K. (2004). Structure and function of choline kinase isoforms in mammalian cells. Prog. Lipid Res. 43, 266-281.
4. Arora, P., Cuevas, B. D., Russo, A., Johnson, G. L. and Trejo, J. (2008). Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasion. Oncogene 27, 4434-4445.
5. Asakura, M., Kitakaze, M., Takashima, S., Liao, Y., Ishikura, F., Yoshinaka, T., Ohmoto, H., Node, K., Yoshino, K., Ishiguro, H. et al. (2002). Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Nat. Med. 8, 35-40.
6. Bence, K., Ma, W., Kozasa, T. and Huang, X. Y. (1997). Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit. Nature 389, 296-299.
7. Birmingham, A., Selfors, L. M., Forster, T., Wrobel, D., Kennedy, C. J., Shanks, E., Santoyo-Lopez, J., Dunican, D. J., Long, A., Kelleher, D. et al. (2009). Statistical methods for analysis of high-throughput RNA interference screens. Nat. Methods 6, 569-575.
8. Chan, H. W., Jenkins, A., Pipolo, L., Hannan, R. D., Thomas, W. G. and Smith, N. J. (2006). Effect of dominant-negative epidermal growth factor receptors on cardiomyocyte hypertrophy. J. Recept. Signal Transduct. Res. 26, 659-677.
9. Clem, B. F., Clem, A. L., Yalcin, A., Goswami, U., Arumugam, S., Telang, S., Trent, J. O. and Chesney, J. (2011). A novel small molecule antagonist of choline kinase-a that simultaneously suppresses MAPK and PI3K/AKT signaling. Oncogene 30, 3370-3380.
10. Cohen, I., Maoz, M., Turm, H., Grisaru-Granovsky, S., Maly, B., Uziely, B., Weiss, E., Abramovitch, R., Gross, E., Barzilay, O. et al. (2010). Etk/Bmx regulates proteinase-activated-receptor1 (PAR1) in breast cancer invasion: signaling partners, hierarchy and physiological significance. PLoS ONE 5, e11135.
11. Dai, B., Kim, O., Xie, Y., Guo, Z., Xu, K., Wang, B., Kong, X., Melamed, J., Chen, H., Bieberich, C. J. et al. (2006). Tyrosine kinase Etk/BMX is up-regulated in human prostate cancer and its overexpression induces prostate intraepithelial neoplasia in mouse. Cancer Res. 66, 8058-8064.
12. Daub, H., Weiss, F. U., Wallasch, C. and Ullrich, A. (1996). Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 379, 557-560.
13. de Gasparo, M., Catt, K. J., Inagami, T., Wright, J. W. and Unger, T. (2000). International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol. Rev. 52, 415-472.
14. De Paepe, B., Verstraeten, V. L., De Potter, C. R., Vakaet, L. A. and Bullock, G. R. (2001). Growth stimulatory angiotensin II type-1 receptor is upregulated in breast hyperplasia and in situ carcinoma but not in invasive carcinoma. Histochem. Cell Biol. 116, 247-254.
15. Debant, A., Serra-Pages, C., Seipel, K., O'Brien, S., Tang, M., Park, S. H. and Streuli, M. (1996). The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc. Natl. Acad. Sci. USA 93, 5466-5471.
16. Eguchi, S., Numaguchi, K., Iwasaki, H., Matsumoto, T., Yamakawa, T., Utsunomiya, H., Motley, E. D., Kawakatsu, H., Owada, K. M., Hirata, Y. et al. (1998). Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. J. Biol. Chem. 273, 8890-8896.
17. Eguchi, S., Iwasaki, H., Inagami, T., Numaguchi, K., Yamakawa, T., Motley, E. D., Owada, K. M., Marumo, F. and Hirata, Y. (1999). Involvement of PYK2 in angiotensin II signaling of vascular smooth muscle cells. Hypertension 33, 201-206.
18. Eguchi, S., Dempsey, P. J., Frank, G. D., Motley, E. D. and Inagami, T. (2001). Activation of MAPKs by angiotensin II in vascular smooth muscle cells. Metalloprotease-dependent EGF receptor activation is required for activation of ERK and p38 MAPK but not for JNK. J. Biol. Chem. 276, 7957-7962.
19. Ekman, N., Lymboussaki, A., Västrik, I., Sarvas, K., Kaipainen, A. and Alitalo, K. (1997). Bmx tyrosine kinase is specifically expressed in the endocardium and the endothelium of large arteries. Circulation 96, 1729-1732.
20. Elenbaas, B., Spirio, L., Koerner, F., Fleming, M. D., Zimonjic, D. B., Donaher, J. L., Popescu, N. C., Hahn, W. C. and Weinberg, R. A. (2001). Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev. 15, 50-65.
21. Gao, Y., Dickerson, J. B., Guo, F., Zheng, J. and Zheng, Y. (2004). Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc. Natl. Acad. Sci. USA 101, 7618-7623.
22. George, A. J., Thomas, W. G. and Hannan, R. D. (2010). The renin-angiotensin system and cancer: old dog, new tricks. Nat. Rev. Cancer 10, 745-759.
23. Glunde, K., Shah, T., Winnard, P. T., Jr, Raman, V., Takagi, T., Vesuna, F., Artemov, D. and Bhujwalla, Z. M. (2008). Hypoxia regulates choline kinase expression through hypoxia-inducible factor-1 alpha signaling in a human prostate cancer model. Cancer Res. 68, 172-180.
24. Greco, S., Muscella, A., Elia, M. G., Salvatore, P., Storelli, C., Mazzotta, A., Manca, C. and Marsigliante, S. (2003). Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells. J. Cell. Physiol. 196, 370-377.
25. Guilluy, C., Brégeon, J., Toumaniantz, G., Rolli-Derkinderen, M., Retailleau, K., Loufrani, L., Henrion, D., Scalbert, E., Bril, A., Torres, R. M. et al. (2010). The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat. Med. 16, 183-190.
26. Guo, S., Sun, F., Guo, Z., Li, W., Alfano, A., Chen, H., Magyar, C. E., Huang, J., Chai, T. C., Qiu, S. et al. (2011). Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy. PLoS ONE 6, e17778.
27. Heringer-Walther, S., Eckert, K., Schumacher, S. M., Uharek, L., Wulf-Goldenberg, A., Gembardt, F., Fichtner, I., Schultheiss, H. P., Rodgers, K. and Walther, T. (2009). Angiotensin-(1-7) stimulates hematopoietic progenitor cells in vitro and in vivo. Haematologica 94, 857-860.
28. Hernando, E., Sarmentero-Estrada, J., Koppie, T., Belda-Iniesta, C., Ramírez de Molina, V., Cejas, P., Ozu, C., Le, C., Sánchez, J. J., González-Barón, M. et al. (2009). A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas. Oncogene 28, 2425-2435.
29. Hitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J. and Yuan, J. (2008). Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135, 1311-1323.
30. Hunyady, L. and Catt, K. J. (2006). Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol. Endocrinol. 20, 953-970.
31. Iwai, M. and Horiuchi, M. (2009). Role of renin-angiotensin system in adipose tissue dysfunction. Hypertens. Res. 32, 425-427.
32. Jiang, X., Borgesi, R. A., McKnight, N. C., Kaur, R., Carpenter, C. L. and Balk, S. P. (2007). Activation of nonreceptor tyrosine kinase Bmx/Etk mediated by phosphoinositide 3-kinase, epidermal growth factor receptor, and ErbB3 in prostate cancer cells. J. Biol. Chem. 282, 32689-32698.
33. Kittler, R., Pelletier, L., Heninger, A. K., Slabicki, M., Theis, M., Miroslaw, L., Poser, I., Lawo, S., Grabner, H., Kozak, K. et al. (2007). Genome-scale RNAi profiling of cell division in human tissue culture cells. Nat. Cell Biol. 9, 1401-1412.
34. Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.
35. Langhans-Rajasekaran, S. A., Wan, Y. and Huang, X. Y. (1995). Activation of Tsk and Btk tyrosine kinases by G protein beta gamma subunits. Proc. Natl. Acad. Sci. USA 92, 8601-8605.
36. Li, N. C., Lee, A., Whitmer, R. A., Kivipelto, M., Lawler, E., Kazis, L. E. and Wolozin, B. (2010). Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 340, b5465.
37. Lu, H., Rateri, D. L., Cassis, L. A. and Daugherty, A. (2008). The role of the reninangiotensin system in aortic aneurysmal diseases. Curr. Hypertens. Rep. 10, 99-106.
38. Lutz, S., Freichel-Blomquist, A., Yang, Y., Rümenapp, U., Jakobs, K. H., Schmidt, M. and Wieland, T. (2005). The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J. Biol. Chem. 280, 11134-11139.
39. Mehta, P. K. and Griendling, K. K. (2007). Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. 292, C82-C97.
40. Mifune, M., Ohtsu, H., Suzuki, H., Nakashima, H., Brailoiu, E., Dun, N. J., Frank, G. D., Inagami, T., Higashiyama, S., Thomas, W. G. et al. (2005). G protein coupling and second messenger generation are indispensable for metalloproteasedependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor. J. Biol. Chem. 280, 26592-26599.
41. Miners, S., Ashby, E., Baig, S., Harrison, R., Tayler, H., Speedy, E., Prince, J. A., Love, S. and Kehoe, P. G. (2009). Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes. Am. J. Transl Res. 1, 163-177.
42. Mitchell-Jordan, S. A., Holopainen, T., Ren, S., Wang, S., Warburton, S., Zhang, M. J., Alitalo, K., Wang, Y. and Vondriska, T. M. (2008). Loss of Bmx nonreceptor tyrosine kinase prevents pressure overload-induced cardiac hypertrophy. Circ. Res. 103, 1359-1362.
43. Miyake, T. and Parsons, S. J. (2012). Functional interactions between Choline kinase a, epidermal growth factor receptor and c-Src in breast cancer cell proliferation. Oncogene 31, 1431-1441.
44. Negro, A., Brar, B. K., Gu, Y., Peterson, K. L., Vale, W. and Lee, K. F. (2006). erbB2 is required for G protein-coupled receptor signaling in the heart. Proc. Natl. Acad. Sci. USA 103, 15889-15893.
45. Ohtsu, H., Dempsey, P. J., Frank, G. D., Brailoiu, E., Higuchi, S., Suzuki, H., Nakashima, H., Eguchi, K. and Eguchi, S. (2006). ADAM17 mediates epidermal growth factor receptor transactivation and vascular smooth muscle cell hypertrophy induced by angiotensin II. Arterioscler. Thromb. Vasc. Biol. 26, e133-e137.
46. Ohtsu, H., Higuchi, S., Shirai, H., Eguchi, K., Suzuki, H., Hinoki, A., Brailoiu, E., Eckhart, A. D., Frank, G. D. and Eguchi, S. (2008). Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells. Endocrinology 149, 3569-3575.
47. Osmond, R. I., Sheehan, A., Borowicz, R., Barnett, E., Harvey, G., Turner, C., Brown, A., Crouch, M. F. and Dyer, A. R. (2005). GPCR screening via ERK 1/2: a novel platform for screening G protein-coupled receptors. J. Biomol. Screen. 10, 730-737.
48. Park, T. S. and Zambidis, E. T. (2009). A role for the renin-angiotensin system in hematopoiesis. Haematologica 94, 745-747.
49. Qian, H., Pipolo, L. and Thomas, W. G. (2001). Association of beta-Arrestin 1 with the type 1A angiotensin II receptor involves phosphorylation of the receptor carboxyl terminus and correlates with receptor internalization. Mol. Endocrinol. 15, 1706-1719.
50. Ramírez de Molina, A., Báñez-Coronel, M., Gutiérrez, R., Rodríguez-González, A., Olmeda, D., Megías, D. and Lacal, J. C. (2004). Choline kinase activation is a critical requirement for the proliferation of primary human mammary epithelial cells and breast tumor progression. Cancer Res. 64, 6732-6739.
51. Rhodes, D. R., Ateeq, B., Cao, Q., Tomlins, S. A., Mehra, R., Laxman, B., Kalyana-Sundaram, S., Lonigro, R. J., Helgeson, B. E., Bhojani, M. S. et al. (2009). AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist. Proc. Natl. Acad. Sci. USA 106, 10284-10289.
52. Rojas, R. J., Yohe, M. E., Gershburg, S., Kawano, T., Kozasa, T. and Sondek, J. (2007). Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain. J. Biol. Chem. 282, 29201-29210.
53. Rompe, F., Unger, T. and Steckelings, U. M. (2010). The angiotensin AT2 receptor in inflammation. Drug News Perspect. 23, 104-111.
54. Rozen, S. and Skaletsky, H. (2000). Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol. 132, 365-386.
55. Schiffrin, E. L. (2010). T lymphocytes: a role in hypertension? Curr. Opin. Nephrol. Hypertens. 19, 181-186.
56. Seta, K. and Sadoshima, J. (2003). Phosphorylation of tyrosine 319 of the angiotensin II type 1 receptor mediates angiotensin II-induced trans-activation of the epidermal growth factor receptor. J. Biol. Chem. 278, 9019-9026.
57. Shah, B. H. and Catt, K. J. (2002). Calcium-independent activation of extracellularly regulated kinases 1 and 2 by angiotensin II in hepatic C9 cells: roles of protein kinase Cdelta, Src/proline-rich tyrosine kinase 2, and epidermal growth receptor transactivation. Mol. Pharmacol. 61, 343-351.
58. Shah, B. H. and Catt, K. J. (2006). TACE-dependent EGF receptor activation in angiotensin-II-induced kidney disease. Trends Pharmacol. Sci. 27, 235-237.
59. Shenoy, S. K. and Lefkowitz, R. J. (2011). b-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol. Sci. 32, 521-533.
60. Simpson, K. J., Selfors, L. M., Bui, J., Reynolds, A., Leake, D., Khvorova, A. and Brugge, J. S. (2008). Identification of genes that regulate epithelial cell migration using an siRNA screening approach. Nat. Cell Biol. 10, 1027-1038.
61. Smith, N. J., Chan, H. W., Qian, H., Bourne, A. M., Hannan, K. M., Warner, F. J., Ritchie, R. H., Pearson, R. B., Hannan, R. D. and Thomas, W. G. (2011). Determination of the exact molecular requirements for type 1 angiotensin receptor epidermal growth factor receptor transactivation and cardiomyocyte hypertrophy. Hypertension 57, 973-980.
62. Szklarczyk, D., Franceschini, A., Kuhn, M., Simonovic, M., Roth, A., Minguez, P., Doerks, T., Stark, M., Muller, J., Bork, P. et al. (2011). The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39, D561-D568.
63. Tahmasebi, M., Barker, S., Puddefoot, J. R. and Vinson, G. P. (2006). Localisation of renin-angiotensin system (RAS) components in breast. Br. J. Cancer 95, 67-74.
64. Tamagnone, L., Lahtinen, I., Mustonen, T., Virtaneva, K., Francis, F., Muscatelli, F., Alitalo, R., Smith, C. I., Larsson, C. and Alitalo, K. (1994). BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2. Oncogene 9, 3683-3688.
65. Thomas, W. G., Motel, T. J., Kule, C. E., Karoor, V. and Baker, K. M. (1998). Phosphorylation of the angiotensin II (AT1A) receptor carboxyl terminus: a role in receptor endocytosis. Mol. Endocrinol. 12, 1513-1524.
66. Thomas, W. G., Brandenburger, Y., Autelitano, D. J., Pham, T., Qian, H. and Hannan, R. D. (2002). Adenoviral-directed expression of the type 1A angiotensin receptor promotes cardiomyocyte hypertrophy via transactivation of the epidermal growth factor receptor. Circ. Res. 90, 135-142.
67. Touyz, R. M., Wu, X. H., He, G., Salomon, S. and Schiffrin, E. L. (2002). Increased angiotensin II-mediated Src signaling via epidermal growth factor receptor transactivation is associated with decreased C-terminal Src kinase activity in vascular smooth muscle cells from spontaneously hypertensive rats. Hypertension 39, 479-485.
68. Tsukada, S., Simon, M. I., Witte, O. N. and Katz, A. (1994). Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase. Proc. Natl. Acad. Sci. USA 91, 11256-11260.
69. Uchiyama, K., Saito, M., Sasaki, M., Obara, Y., Higashiyama, S. and Nakahata, N. (2009). Thromboxane A2 receptor-mediated epidermal growth factor receptor transactivation: involvement of PKC-delta and PKC-epsilon in the shedding of epidermal growth factor receptor ligands. Eur. J. Pharm. Sci. 38, 504-511.
70. Uchiyama-Tanaka, Y., Matsubara, H., Nozawa, Y., Murasawa, S., Mori, Y., Kosaki, A., Maruyama, K., Masaki, H., Shibasaki, Y., Fujiyama, S. et al. (2001). Angiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells. Kidney Int. 60, 2153-2163.
71. Vaqué, J. P., Dorsam, R. T., Feng, X., Iglesias-Bartolome, R., Forsthoefel, D. J., Chen, Q., Debant, A., Seeger, M. A., Ksander, B. R., Teramoto, H. et al. (2013). A genome-wide RNAi screen reveals a Trio-regulated Rho GTPase circuitry transducing mitogenic signals initiated by G protein-coupled receptors. Mol. Cell 49, 94-108.
72. Wang, Y., Xiao, J., Suzek, T. O., Zhang, J., Wang, J., Zhou, Z., Han, L., Karapetyan, K., Dracheva, S., Shoemaker, B. A. et al. (2012). PubChem's BioAssay Database. Nucleic Acids Res 40, D400-D412.
73. Weiss, D., Sorescu, D. and Taylor, W. R. (2001). Angiotensin II and atherosclerosis. Am. J. Cardiol. 87 Suppl., 25C-32C.
74. Wettschureck, N., Rütten, H., Zywietz, A., Gehring, D., Wilkie, T. M., Chen, J., Chien, K. R. and Offermanns, S. (2001). Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. Nat. Med. 7, 1236-1240.
75. Williams, S. L., Lutz, S., Charlie, N. K., Vettel, C., Ailion, M., Coco, C., Tesmer, J. J., Jorgensen, E. M., Wieland, T. and Miller, K. G. (2007). Trio's Rho-specific GEF domain is the missing Galpha q effector in C. elegans. Genes Dev. 21, 2731-2746.
76. Wu, G., Aoyama, C., Young, S. G. and Vance, D. E. (2008). Early embryonic lethality caused by disruption of the gene for choline kinase alpha, the first enzyme in phosphatidylcholine biosynthesis. J. Biol. Chem. 283, 1456-1462.
77. Yalcin, A., Clem, B., Makoni, S., Clem, A., Nelson, K., Thornburg, J., Siow, D., Lane, A. N., Brock, S. E., Goswami, U. et al. (2010). Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling. Oncogene 29, 139-149.
78. Zambidis, E. T., Park, T. S., Yu, W., Tam, A., Levine, M., Yuan, X., Pryzhkova, M. and Péault, B. (2008). Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells. Blood 112, 3601-3614.