{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:36:58Z","timestamp":1790379418946,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T00:00:00Z","timestamp":1417737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T00:00:00Z","timestamp":1417737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glioblastoma (GBM), the most common type of primary malignant brain tumors harboring a subpopulation of stem-like cells (GSCs), is a fast-growing and often fatal tumor. Signal Transducer and Activator of Transcription 3 (STAT3) is one of the major signaling pathways in GSCs maintenance but the molecular mechanisms underlying STAT3 deregulation in GSCs are poorly defined. Here, we demonstrate that Inositol Polyphosphate-5-Phosphatase F (INPP5F), one of the polyphosphoinositide phosphatases, is differentially expressed in GSCs from glioma patients and is identified as an inhibitor of STAT3 signaling via interaction with STAT3 and inhibition of its phosphorylation. Constitutively expressed INPP5F showed to suppress self-renewal and proliferation potentials of glioblastoma cells and reduced tumorigenicity of glioblastoma. In addition, loss of\n                    <jats:italic>INPP5F<\/jats:italic>\n                    gene in gliomas is significantly correlated with lower overall patient survivals. These findings suggest that INPP5F is a potential tumor suppressor in gliomas via inhibition of STAT3 pathway and that deregulation of INPP5F may lead to contribution to gliomagenesis.\n                  <\/jats:p>","DOI":"10.1038\/srep07330","type":"journal-article","created":{"date-parts":[[2014,12,5]],"date-time":"2014-12-05T05:09:42Z","timestamp":1417756182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity"],"prefix":"10.1038","volume":"4","author":[{"given":"Hong Sug","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susie","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,12,5]]},"reference":[{"key":"BFsrep07330_CR1","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1056\/NEJMoa1308573","volume":"370","author":"MR Gilbert","year":"2014","unstructured":"Gilbert, M. R. et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370, 699\u2013708 (2014).","journal-title":"N Engl J Med"},{"key":"BFsrep07330_CR2","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.2353\/ajpath.2007.070011","volume":"170","author":"H Ohgaki","year":"2007","unstructured":"Ohgaki, H. & Kleihues, P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170, 1445\u20131453 (2007).","journal-title":"Am J Pathol"},{"key":"BFsrep07330_CR3","doi-asserted-by":"publisher","first-page":"22011","DOI":"10.1074\/jbc.M101579200","volume":"276","author":"T Minagawa","year":"2001","unstructured":"Minagawa, T., Ijuin, T., Mochizuki, Y. & Takenawa, T. Identification and characterization of a sac domain-containing phosphoinositide 5-phosphatase. J Biol Chem 276, 22011\u201322015 (2001).","journal-title":"J Biol Chem"},{"key":"BFsrep07330_CR4","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nm1552","volume":"13","author":"CM Trivedi","year":"2007","unstructured":"Trivedi, C. M. et al. Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med 13, 324\u2013331 (2007).","journal-title":"Nat Med"},{"key":"BFsrep07330_CR5","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1161\/CIRCRESAHA.109.208785","volume":"105","author":"W Zhu","year":"2009","unstructured":"Zhu, W. et al. Inpp5f is a polyphosphoinositide phosphatase that regulates cardiac hypertrophic responsiveness. Circ Res 105, 1240\u20131247 (2009).","journal-title":"Circ Res"},{"key":"BFsrep07330_CR6","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1007\/BF03403538","volume":"5","author":"DA Frank","year":"1999","unstructured":"Frank, D. A. STAT signaling in the pathogenesis and treatment of cancer. Mol Med 5, 432\u2013456 (1999).","journal-title":"Mol Med"},{"key":"BFsrep07330_CR7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.canlet.2006.10.017","volume":"251","author":"DA Frank","year":"2007","unstructured":"Frank, D. A. STAT3 as a central mediator of neoplastic cellular transformation. Cancer Lett 251, 199\u2013210 (2007).","journal-title":"Cancer Lett"},{"key":"BFsrep07330_CR8","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1128\/MCB.18.5.2553","volume":"18","author":"JF Bromberg","year":"1998","unstructured":"Bromberg, J. F., Horvath, C. M., Besser, D., Lathem, W. W. & Darnell, J. E., Jr Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol 18, 2553\u20132558 (1998).","journal-title":"Mol Cell Biol"},{"key":"BFsrep07330_CR9","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1128\/MCB.18.5.2545","volume":"18","author":"J Turkson","year":"1998","unstructured":"Turkson, J. et al. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol 18, 2545\u20132552 (1998).","journal-title":"Mol Cell Biol"},{"key":"BFsrep07330_CR10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0092-8674(00)81959-5","volume":"98","author":"JF Bromberg","year":"1999","unstructured":"Bromberg, J. F. et al. Stat3 as an oncogene. Cell 98, 295\u2013303 (1999).","journal-title":"Cell"},{"key":"BFsrep07330_CR11","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/nri1885","volume":"6","author":"NC Reich","year":"2006","unstructured":"Reich, N. C. & Liu, L. Tracking STAT nuclear traffic. Nat Rev Immunol 6, 602\u2013612 (2006).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep07330_CR12","doi-asserted-by":"publisher","first-page":"29252","DOI":"10.1074\/jbc.M304196200","volume":"278","author":"J Ma","year":"2003","unstructured":"Ma, J., Zhang, T., Novotny-Diermayr, V., Tan, A. L. & Cao, X. A novel sequence in the coiled-coil domain of Stat3 essential for its nuclear translocation. J Biol Chem 278, 29252\u201329260 (2003).","journal-title":"J Biol Chem"},{"key":"BFsrep07330_CR13","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.cellsig.2005.06.016","volume":"18","author":"J Ma","year":"2006","unstructured":"Ma, J. & Cao, X. Regulation of Stat3 nuclear import by importin alpha5 and importin alpha7 via two different functional sequence elements. Cell Signal 18, 1117\u20131126 (2006).","journal-title":"Cell Signal"},{"key":"BFsrep07330_CR14","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/nature07385","volume":"455","author":"TCGAR Network","year":"2008","unstructured":"Network, T. C. G. A. R. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061\u20131068 (2008).","journal-title":"Nature"},{"key":"BFsrep07330_CR15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1158\/1541-7786.MCR-08-0435","volume":"7","author":"S Madhavan","year":"2009","unstructured":"Madhavan, S. et al. Rembrandt: helping personalized medicine become a reality through integrative translational research. Mol Cancer Res 7, 157\u2013167 (2009).","journal-title":"Mol Cancer Res"},{"key":"BFsrep07330_CR16","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","volume":"277","author":"JE Darnell Jr","year":"1997","unstructured":"Darnell, J. E., Jr STATs and gene regulation. Science 277, 1630\u20131635 (1997).","journal-title":"Science"},{"key":"BFsrep07330_CR17","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1749-6632.2009.04911.x","volume":"1171","author":"BB Aggarwal","year":"2009","unstructured":"Aggarwal, B. B. et al. Signal transducer and activator of transcription-3, inflammation and cancer: how intimate is the relationship? Ann N Y Acad Sci 1171, 59\u201376 (2009).","journal-title":"Ann N Y Acad Sci"},{"key":"BFsrep07330_CR18","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nrg1879","volume":"7","author":"JA Engelman","year":"2006","unstructured":"Engelman, J. A., Luo, J. & Cantley, L. C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7, 606\u2013619 (2006).","journal-title":"Nat Rev Genet"},{"key":"BFsrep07330_CR19","doi-asserted-by":"publisher","first-page":"13375","DOI":"10.1074\/jbc.273.22.13375","volume":"273","author":"T Maehama","year":"1998","unstructured":"Maehama, T. & Dixon, J. E. The tumor suppressor, PTEN\/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273, 13375\u201313378 (1998).","journal-title":"J Biol Chem"},{"key":"BFsrep07330_CR20","doi-asserted-by":"publisher","first-page":"9027","DOI":"10.1074\/jbc.M106755200","volume":"277","author":"MP Scheid","year":"2002","unstructured":"Scheid, M. P. et al. Phosphatidylinositol (3,4,5)P3 is essential but not sufficient for protein kinase B (PKB) activation; phosphatidylinositol (3,4)P2 is required for PKB phosphorylation at Ser-473: studies using cells from SH2-containing inositol-5-phosphatase knockout mice. J Biol Chem 277, 9027\u20139035 (2002).","journal-title":"J Biol Chem"},{"key":"BFsrep07330_CR21","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1158\/2159-8290.CD-11-0218","volume":"1","author":"PK Vogt","year":"2011","unstructured":"Vogt, P. K. & Hart, J. R. PI3K and STAT3: a new alliance. Cancer Discov 1, 481\u2013486 (2011).","journal-title":"Cancer Discov"},{"key":"BFsrep07330_CR22","doi-asserted-by":"publisher","first-page":"8404","DOI":"10.1038\/sj.onc.1206047","volume":"21","author":"SO Rahaman","year":"2002","unstructured":"Rahaman, S. O. et al. Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene 21, 8404\u20138413 (2002).","journal-title":"Oncogene"},{"key":"BFsrep07330_CR23","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.stem.2010.06.022","volume":"7","author":"J Yang","year":"2010","unstructured":"Yang, J. et al. Stat3 activation is limiting for reprogramming to ground state pluripotency. Cell Stem Cell 7, 319\u2013328 (2010).","journal-title":"Cell Stem Cell"},{"key":"BFsrep07330_CR24","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/nrm909","volume":"3","author":"DE Levy","year":"2002","unstructured":"Levy, D. E. & Darnell, J. E., Jr Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3, 651\u2013662 (2002).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFsrep07330_CR25","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ccr.2009.01.001","volume":"15","author":"S Grivennikov","year":"2009","unstructured":"Grivennikov, S. et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15, 103\u2013113 (2009).","journal-title":"Cancer Cell"},{"key":"BFsrep07330_CR26","doi-asserted-by":"publisher","first-page":"580","DOI":"10.2174\/156652409788488739","volume":"9","author":"N de la Iglesia","year":"2009","unstructured":"de la Iglesia, N., Puram, S. V. & Bonni, A. STAT3 regulation of glioblastoma pathogenesis. Curr Mol Med 9, 580\u2013590 (2009).","journal-title":"Curr Mol Med"},{"key":"BFsrep07330_CR27","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1002\/stem.185","volume":"27","author":"MM Sherry","year":"2009","unstructured":"Sherry, M. M., Reeves, A., Wu, J. K. & Cochran, B. H. STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells 27, 2383\u20132392 (2009).","journal-title":"Stem Cells"},{"key":"BFsrep07330_CR28","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1126\/science.278.5344.1803","volume":"278","author":"CD Chung","year":"1997","unstructured":"Chung, C. D. et al. Specific inhibition of Stat3 signal transduction by PIAS3. Science 278, 1803\u20131805 (1997).","journal-title":"Science"},{"key":"BFsrep07330_CR29","doi-asserted-by":"publisher","first-page":"9435","DOI":"10.1073\/pnas.0900571106","volume":"106","author":"S Veeriah","year":"2009","unstructured":"Veeriah, S. et al. The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci U S A 106, 9435\u20139440 (2009).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep07330_CR30","doi-asserted-by":"publisher","first-page":"32689","DOI":"10.1074\/jbc.M703412200","volume":"282","author":"X Jiang","year":"2007","unstructured":"Jiang, X. et al. 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\u201332698 (2007).","journal-title":"J Biol Chem"},{"key":"BFsrep07330_CR31","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.ccr.2011.03.004","volume":"19","author":"OA Guryanova","year":"2011","unstructured":"Guryanova, O. A. et al. Nonreceptor tyrosine kinase BMX maintains self-renewal and tumorigenic potential of glioblastoma stem cells by activating STAT3. Cancer Cell 19, 498\u2013511 (2011).","journal-title":"Cancer Cell"},{"key":"BFsrep07330_CR32","doi-asserted-by":"publisher","first-page":"7132","DOI":"10.1128\/MCB.20.19.7132-7139.2000","volume":"20","author":"T Zhang","year":"2000","unstructured":"Zhang, T., Kee, W. H., Seow, K. T., Fung, W. & Cao, X. The coiled-coil domain of Stat3 is essential for its SH2 domain-mediated receptor binding and subsequent activation induced by epidermal growth factor and interleukin-6. Mol Cell Biol 20, 7132\u20137139 (2000).","journal-title":"Mol Cell Biol"},{"key":"BFsrep07330_CR33","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.ccr.2013.04.008","volume":"23","author":"E Kim","year":"2013","unstructured":"Kim, E. et al. Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. Cancer Cell 23, 839\u2013852 (2013).","journal-title":"Cancer Cell"},{"key":"BFsrep07330_CR34","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.ccr.2006.03.030","volume":"9","author":"J Lee","year":"2006","unstructured":"Lee, J. et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 9, 391\u2013403 (2006).","journal-title":"Cancer Cell"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep07330.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep07330","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep07330.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:57:23Z","timestamp":1672966643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep07330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,5]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,12,17]]}},"alternative-id":["BFsrep07330"],"URL":"https:\/\/doi.org\/10.1038\/srep07330","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,5]]},"assertion":[{"value":"8 August 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7330"}}