Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

YAP and MRTF-A, transcriptional co-activators of RhoA-mediated gene expression, are critical for glioblastoma tumorigenicity


The role of YAP (Yes-associated protein 1) and MRTF-A (myocardin-related transcription factor A), two transcriptional co-activators regulated downstream of GPCRs (G protein-coupled receptors) and RhoA, in the growth of glioblastoma cells and in vivo glioblastoma multiforme (GBM) tumor development was explored using human glioblastoma cell lines and tumor-initiating cells derived from patient-derived xenografts (PDX). Knockdown of these co-activators in GSC-23 PDX cells using short hairpin RNA significantly attenuated in vitro self-renewal capability assessed by limiting dilution, oncogene expression, and neurosphere formation. Orthotopic xenografts of the MRTF-A and YAP knockdown PDX cells formed significantly smaller tumors and were of lower morbidity than wild-type cells. In vitro studies used PDX and 1321N1 glioblastoma cells to examine functional responses to sphingosine 1-phosphate (S1P), a GPCR agonist that activates RhoA signaling, demonstrated that YAP signaling was required for cell migration and invasion, whereas MRTF-A was required for cell adhesion; both YAP and MRTF-A were required for proliferation. Gene expression analysis by RNA-sequencing of S1P-treated MRTF-A or YAP knockout cells identified 44 genes that were induced through RhoA and highly dependent on YAP, MRTF-A, or both. Knockdown of F3 (tissue factor (TF)), a target gene regulated selectively through YAP, blocked cell invasion and migration, whereas knockdown of HBEGF (heparin-binding epidermal growth factor-like growth factor), a gene selectively induced through MRTF-A, prevented cell adhesion in response to S1P. Proliferation was sensitive to knockdown of target genes regulated through either or both YAP and MRTF-A. Expression of TF and HBEGF was also selectively decreased in tumors from PDX cells lacking YAP or MRTF-A, indicating that these transcriptional pathways are regulated in preclinical GBM models and suggesting that their activation through GPCRs and RhoA contributes to growth and maintenance of human GBM.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. 1.

    Fukuhara S, Chikumi H, Gutkind JS. Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho. FEBS Lett. 2000;485:183–8.

    CAS  Article  Google Scholar 

  2. 2.

    Jiang H, Wu D, Simon MI. The transforming activity of activated G alpha 12. FEBS Lett. 1993;330:319–22.

    CAS  Article  Google Scholar 

  3. 3.

    Reuther GW, Lambert QT, Booden MA, Wennerberg K, Becknell B, Marcucci G, et al. Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl family protein found mutated in leukemia, causes transformation by activation of RhoA. J Biol Chem. 2001;276:27145–51.

    CAS  Article  Google Scholar 

  4. 4.

    Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer. 2002;2:133–42.

    Article  Google Scholar 

  5. 5.

    Toksoz D, Williams DA. Novel human oncogene lbc detected by transfection with distinct homology regions to signal transduction products. Oncogene. 1994;9:621–8.

    CAS  PubMed  Google Scholar 

  6. 6.

    Xu N, Bradley L, Ambdukar I, Gutkind JS. A mutant alpha subunit of G12 potentiates the eicosanoid pathway and is highly oncogenic in NIH 3T3 cells. Proc Natl Acad Sci USA. 1993;90:6741–5.

    CAS  Article  Google Scholar 

  7. 7.

    Fortin Ensign SP, Mathews IT, Symons MH, Berens ME, Tran NL. Implications of Rho GTPase signaling in glioma cell invasion and tumor progression. Front Oncol. 2013;3:241.

    Article  Google Scholar 

  8. 8.

    Juneja J, Casey PJ. Role of G12 proteins in oncogenesis and metastasis. Br J Pharmacol. 2009;158:32–40.

    CAS  Article  Google Scholar 

  9. 9.

    Post GR, Collins LR, Kennedy ED, Moskowitz SA, Aragay AM, Goldstein D, et al. Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells. Mol Biol Cell. 1996;7:1679–90.

    CAS  Article  Google Scholar 

  10. 10.

    Walsh CT, Radeff-Huang J, Matteo R, Hsiao A, Subramaniam S, Stupack D, et al. Thrombin receptor and RhoA mediate cell proliferation through integrins and cysteine-rich protein 61. FASEB J. 2008;22:4011–21.

    CAS  Article  Google Scholar 

  11. 11.

    Yu OM, Brown JH. G protein-coupled receptor and RhoA-stimulated transcriptional responses: links to inflammation, differentiation, and cell proliferation. Mol Pharmacol. 2015;88:171–80.

    CAS  Article  Google Scholar 

  12. 12.

    Qiu RG, Chen J, McCormick F, Symons M. A role for Rho in Ras transformation. Proc Natl Acad Sci USA. 1995;92:11781–5.

    CAS  Article  Google Scholar 

  13. 13.

    Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell. 2014;25:831–45.

    CAS  Article  Google Scholar 

  14. 14.

    Rossol-Allison J, Stemmle LN, Swenson-Fields KI, Kelly P, Fields PE, McCall SJ, et al. Rho GTPase activity modulates Wnt3a/beta-catenin signaling. Cell Signal. 2009;21:1559–68.

    CAS  Article  Google Scholar 

  15. 15.

    Park HW, Kim YC, Yu B, Moroishi T, Mo JS, Plouffe SW, et al. Alternative Wnt signaling activates YAP/TAZ. Cell. 2015;162:780–94.

    CAS  Article  Google Scholar 

  16. 16.

    Hill CS, Wynne J, Treisman R. The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. Cell. 1995;81:1159–70.

    CAS  Article  Google Scholar 

  17. 17.

    Sahai E, Alberts AS, Treisman R. RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J. 1998;17:1350–61.

    CAS  Article  Google Scholar 

  18. 18.

    Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, et al. Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes. Mol Cell Biol. 2003;23:6597–608.

    CAS  Article  Google Scholar 

  19. 19.

    Miralles F, Posern G, Zaromytidou AI, Treisman R. Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell. 2003;113:329–42.

    CAS  Article  Google Scholar 

  20. 20.

    Cen B, Selvaraj A, Prywes R. Myocardin/MKL family of SRF coactivators: key regulators of immediate early and muscle specific gene expression. J Cell Biochem. 2004;93:74–82.

    CAS  Article  Google Scholar 

  21. 21.

    Guettler S, Vartiainen MK, Miralles F, Larijani B, Treisman R. RPEL motifs link the serum response factor cofactor MAL but not myocardin to Rho signaling via actin binding. Mol Cell Biol. 2008;28:732–42.

    CAS  Article  Google Scholar 

  22. 22.

    Feng X, Liu P, Zhou X, Li MT, Li FL, Wang Z, et al. Thromboxane A2 activates YAP/TAZ protein to induce vascular smooth muscle cell proliferation and migration. J Biol Chem. 2016;291:18947–58.

    CAS  Article  Google Scholar 

  23. 23.

    Mo JS, Yu FX, Gong R, Brown JH, Guan KL. Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev. 2012;26:2138–43.

    CAS  Article  Google Scholar 

  24. 24.

    Yu FX, Luo J, Mo JS, Liu G, Kim YC, Meng Z, et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell. 2014;25:822–30.

    CAS  Article  Google Scholar 

  25. 25.

    Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, et al. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 2012;150:780–91.

    CAS  Article  Google Scholar 

  26. 26.

    Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F, Elvassore N, et al. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell. 2013;154:1047–59.

    CAS  Article  Google Scholar 

  27. 27.

    Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179–83.

    CAS  Article  Google Scholar 

  28. 28.

    Zhao B, Ye X, Yu J, Li L, Li W, Li S, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008;22:1962–71.

    CAS  Article  Google Scholar 

  29. 29.

    Zhao B, Kim J, Ye X, Lai ZC, Guan KL. Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein. Cancer Res. 2009;69:1089–98.

    CAS  Article  Google Scholar 

  30. 30.

    Yu OM, Miyamoto S, Brown JH. Myocardin-related transcription factor A and Yes-associated protein exert dual control in G protein-coupled receptor- and RhoA-mediated transcriptional regulation and cell proliferation. Mol Cell Biol. 2016;36:39–49.

    CAS  PubMed  Google Scholar 

  31. 31.

    Ponten J, Macintyre EH. Long term culture of normal and neoplastic human glia. Acta Pathol Microbiol Scand. 1968;74:465–86.

    CAS  Article  Google Scholar 

  32. 32.

    Cui Y, Hameed FM, Yang B, Lee K, Pan CQ, Park S, et al. Cyclic stretching of soft substrates induces spreading and growth. Nat Commun. 2015;6:6333.

    CAS  Article  Google Scholar 

  33. 33.

    Chen HI, Sudol M. The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proc Natl Acad Sci USA. 1995;92:7819–23.

    CAS  Article  Google Scholar 

  34. 34.

    Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155:462–77.

    CAS  Article  Google Scholar 

  35. 35.

    Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061–8.

  36. 36.

    Khosravi-Far R, Solski PA, Clark GJ, Kinch MS, Der CJ. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol. 1995;15:6443–53.

    CAS  Article  Google Scholar 

  37. 37.

    Olson MF, Ashworth A, Hall A. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1. Science. 1995;269:1270–2.

    CAS  Article  Google Scholar 

  38. 38.

    Martin CB, Mahon GM, Klinger MB, Kay RJ, Symons M, Der CJ, et al. The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways. Oncogene. 2001;20:1953–63.

    CAS  Article  Google Scholar 

  39. 39.

    Anelli V, Gault CR, Cheng AB, Obeid LM. Sphingosine kinase 1 is upregulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2. J Biol Chem. 2008;283:3365–75.

    CAS  Article  Google Scholar 

  40. 40.

    Bien-Moller S, Lange S, Holm T, Bohm A, Paland H, Kupper J, et al. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme. Oncotarget. 2016;7:13031–46.

    Article  Google Scholar 

  41. 41.

    Kapitonov D, Allegood JC, Mitchell C, Hait NC, Almenara JA, Adams JK, et al. Targeting sphingosine kinase 1 inhibits Akt signaling, induces apoptosis, and suppresses growth of human glioblastoma cells and xenografts. Cancer Res. 2009;69:6915–23.

    CAS  Article  Google Scholar 

  42. 42.

    Hua Y, Tang L, Keep RF, Schallert T, Fewel ME, Muraszko KM, et al. The role of thrombin in gliomas. J Thromb Haemost. 2005;3:1917–23.

    CAS  Article  Google Scholar 

  43. 43.

    Nierodzik ML, Karpatkin S. Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell. 2006;10:355–62.

    CAS  Article  Google Scholar 

  44. 44.

    Kishi Y, Okudaira S, Tanaka M, Hama K, Shida D, Kitayama J, et al. Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem. 2006;281:17492–17500.

    CAS  Article  Google Scholar 

  45. 45.

    Houben AJ, Moolenaar WH. Autotaxin and LPA receptor signaling in cancer. Cancer Metastasis Rev. 2011;30:557–65.

    CAS  Article  Google Scholar 

  46. 46.

    Sarkaria JN, Yang L, Grogan PT, Kitange GJ, Carlson BL, Schroeder MA, et al. Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Mol Cancer Ther. 2007;6:1167–74.

    CAS  Article  Google Scholar 

  47. 47.

    Sarkaria JN, Carlson BL, Schroeder MA, Grogan P, Brown PD, Giannini C, et al. Use of an orthotopic xenograft model for assessing the effect of epidermal growth factor receptor amplification on glioblastoma radiation response. Clin Cancer Res. 2006;12:2264–71.

    CAS  Article  Google Scholar 

  48. 48.

    Giannini C, Sarkaria JN, Saito A, Uhm JH, Galanis E, Carlson BL, et al. Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro Oncol. 2005;7:164–76.

    CAS  Article  Google Scholar 

  49. 49.

    Balasubramaniyan V, Vaillant B, Wang S, Gumin J, Butalid ME, Sai K, et al. Aberrant mesenchymal differentiation of glioma stem-like cells: implications for therapeutic targeting. Oncotarget. 2015;6:31007–17.

    Article  Google Scholar 

  50. 50.

    Suva ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science. 2013;339:1567–70.

    CAS  Article  Google Scholar 

  51. 51.

    Zanconato F, Cordenonsi M, Piccolo S. YAP/TAZ at the roots of cancer. Cancer Cell. 2016;29:783–803.

    CAS  Article  Google Scholar 

  52. 52.

    Esnault C, Stewart A, Gualdrini F, East P, Horswell S, Matthews N, et al. Rho-actin signaling to the MRTF coactivators dominates the immediate transcriptional response to serum in fibroblasts. Genes Dev. 2014;28:943–58.

    CAS  Article  Google Scholar 

  53. 53.

    Mishima K, Higashiyama S, Asai A, Yamaoka K, Nagashima Y, Taniguchi N, et al. Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas. Acta Neuropathol. 1998;96:322–8.

    CAS  Article  Google Scholar 

  54. 54.

    Yotsumoto F, Yagi H, Suzuki SO, Oki E, Tsujioka H, Hachisuga T, et al. Validation of HB-EGF and amphiregulin as targets for human cancer therapy. Biochem Biophys Res Commun. 2008;365:555–61.

    CAS  Article  Google Scholar 

  55. 55.

    Li L, Chakraborty S, Yang CR, Hatanpaa KJ, Cipher DJ, Puliyappadamba VT, et al. An EGFR wild type-EGFRvIII-HB-EGF feed-forward loop regulates the activation of EGFRvIII. Oncogene. 2014;33:4253–64.

    CAS  Article  Google Scholar 

  56. 56.

    Hamada K, Kuratsu J, Saitoh Y, Takeshima H, Nishi T, Ushio Y. Expression of tissue factor correlates with grade of malignancy in human glioma. Cancer. 1996;77:1877–83.

    CAS  Article  Google Scholar 

  57. 57.

    Magnus N, Garnier D, Meehan B, McGraw S, Lee TH, Caron M, et al. Tissue factor expression provokes escape from tumor dormancy and leads to genomic alterations. Proc Natl Acad Sci USA. 2014;111:3544–9.

    CAS  Article  Google Scholar 

  58. 58.

    Magnus N, Meehan B, Garnier D, Hashemi M, Montermini L, Lee TH, et al. The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis. Biochem Biophys Res Commun. 2014;454:262–8.

    CAS  Article  Google Scholar 

  59. 59.

    Quan T, Xu Y, Qin Z, Robichaud P, Betcher S, Calderone K, et al. Elevated YAP and its downstream targets CCN1 and CCN2 in basal cell carcinoma: impact on keratinocyte proliferation and stromal cell activation. Am J Pathol. 2014;184:937–43.

    CAS  Article  Google Scholar 

  60. 60.

    Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, et al. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nat Commun. 2014;5:4632.

    CAS  Article  Google Scholar 

  61. 61.

    Cheng G, Zhang H, Zhang L, Zhang J. Cyr61 promotes growth of glioblastoma in vitro and in vivo. Tumour Biol. 2015;36:2869–73.

    CAS  Article  Google Scholar 

  62. 62.

    Haseley A, Boone S, Wojton J, Yu L, Yoo JY, Yu J, et al. Extracellular matrix protein CCN1 limits oncolytic efficacy in glioma. Cancer Res. 2012;72:1353–62.

    CAS  Article  Google Scholar 

  63. 63.

    Xie D, Yin D, Wang HJ, Liu GT, Elashoff R, Black K, et al. Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas. Clin Cancer Res. 2004;10:2072–81.

    CAS  Article  Google Scholar 

  64. 64.

    Menendez JA, Vellon L, Mehmi I, Teng PK, Griggs DW, Lupu R. A novel CYR61-triggered “CYR61-alphavbeta3 integrin loop” regulates breast cancer cell survival and chemosensitivity through activation of ERK1/ERK2 MAPK signaling pathway. Oncogene. 2005;24:761–79.

    CAS  Article  Google Scholar 

  65. 65.

    Wang J, Wang H, Li Z, Wu Q, Lathia JD, McLendon RE, et al. c-Myc is required for maintenance of glioma cancer stem cells. PLoS ONE. 2008;3:e3769.

    Article  Google Scholar 

  66. 66.

    Plouffe SW, Hong AW, Guan KL. Disease implications of the Hippo/YAP pathway. Trends Mol Med. 2015;21:212–22.

    CAS  Article  Google Scholar 

  67. 67.

    Qiao Y, Chen J, Lim YB, Finch-Edmondson ML, Seshachalam VP, Qin L, et al. YAP regulates actin dynamics through ARHGAP29 and promotes metastasis. Cell Rep. 2017;19:1495–502.

    CAS  Article  Google Scholar 

  68. 68.

    Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol. 2015;17:1218–27.

    CAS  Article  Google Scholar 

  69. 69.

    Shah SR, Tippens N, Park J, Mohyeldin A, Vela G, Martinez-Gutierrez JC, et al. 217 YAP is ready to Rac and Rho: elucidation of a novel YAP-driven network that potentiates brain cancer cell dispersal and confers poor survival in patients. Neurosurgery. 2016;63 Suppl 1:185.

    Article  Google Scholar 

  70. 70.

    Ruf W, Disse J, Carneiro-Lobo TC, Yokota N, Schaffner F. Tissue factor and cell signalling in cancer progression and thrombosis. J Thromb Haemost. 2011;9 Suppl 1:306–15.

    Article  Google Scholar 

  71. 71.

    Rak J, Milsom C, Magnus N, Yu J. Tissue factor in tumour progression. Best Pract Res Clin Haematol. 2009;22:71–83.

    CAS  Article  Google Scholar 

  72. 72.

    Wang S, Reeves B, Pawlinski R. Astrocyte tissue factor controls CNS hemostasis and autoimmune inflammation. Thromb Res. 2016;141 Suppl 2:S65–67.

    CAS  Article  Google Scholar 

  73. 73.

    Gaviglio AL, Knelson EH, Blobe GC. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. FASEB J. 2017;31:1903–15.

    CAS  Article  Google Scholar 

  74. 74.

    Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature. 2014;505:495–501.

    CAS  Article  Google Scholar 

  75. 75.

    Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8:2281–308.

    CAS  Article  Google Scholar 

  76. 76.

    Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.

    CAS  Article  Google Scholar 

  77. 77.

    Siney EJ, Holden A, Casselden E, Bulstrode H, Thomas GJ, Willaime-Morawek S. Metalloproteinases ADAM10 and ADAM17 mediate migration and differentiation in glioblastoma sphere-forming cells. Mol Neurobiol. 2017;54:3893–905.

    CAS  Article  Google Scholar 

  78. 78.

    Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev. 2015;29:1203–17.

    CAS  Article  Google Scholar 

Download references


We thank Jacqueline Sayyah for initial help with culture and analysis of 1321N1 cells, and Silvio Gutkind for assistance with interrogation and analysis of TCGA data

Author contributions

OMY completed much of the experimental work, data analysis, and figure preparation; JAB advised on PDX cell experiments and performed orthotopic xenograft injections; FBF contributed PDX cells and advice on data interpretation; SWP generated the CRISPR knockout cells; DR and AK carried out experiments examining TAZ and MRTF-B involvement; JS generated lentiviral shRNA constructs; KLG advised on manuscript preparation and YAP signaling; BD and JG assisted with RNA-seq and analysis under the direction of AR; OMC contributed studies on cell proliferation and finalized manuscript preparation. SM advised on design of the experiments and analysis of data and contributed to the manuscript preparation; JHB provided overall study supervision, data interpretation, and manuscript preparation.


This work was supported by NIH Grants GM036927, HL028143, HL085577. and CA170682 to JHB; HL097037 to SM; NS080939 to FBF and JAB; AI40127 and AI109842 to AR. OMY and SWP were supported by T32 GM007752; OMY also received support from T32 DK00754; BD is an HHMI postdoctoral fellow from the Jane Coffin Childs Fund; OMC is a PDE fellow from The Brazilian National Council for Scientific and Technological Development.

Author information



Corresponding author

Correspondence to Joan Heller Brown.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yu, O.M., Benitez, J.A., Plouffe, S.W. et al. YAP and MRTF-A, transcriptional co-activators of RhoA-mediated gene expression, are critical for glioblastoma tumorigenicity. Oncogene 37, 5492–5507 (2018).

Download citation

Further reading


Quick links