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| 1 | Analyses of publicly available genomics resources define FGF-2-expressing bladder carcinomas as EMT-prone, proliferative tumors with low mutation rates and high expression of CTLA-4, PD-1 and PD-L1显示文摘Fibroblast growth factor 2(FGF-2)is overexpressed in a subset of invasive bladder carcinomas and its overexpression correlates with poor prognosis.Analyses of publicly available databases addressing the molecular mechanisms that may be responsible for the poor prognosis of these tumors,revealed that FGF-2 expression correlates positively with the expression of epithelial to mesenchymal transition(EMT)-promoting transcription factors and with changes in gene expression that are characteristic of EMT.The same analyses also revealed that FGF-2 correlates negatively with the expression,mutation and copy number variations of FGFR-3,all of which are associated with noninvasive bladder carcinomas.Finally,they showed that FGF-2 expression correlates with the expression of FGFR-1,the expression of the IIIc variant of FGFR-2 and with the expression of Akt3.The latter observation is significant because our earlier studies had shown that Akt3 regulates FGFR-2 alternative splicing,shifting the balance toward the IIIc relative to the IIIb FGFR-2 splice variant.As the IIIc variant is recognized by FGF-2,while the IIIb variant is not,we conclude that Akt3 may facilitate the FGF-2 response.FGF-2 is known to promote the expression of KDM2B,which functions in concert with EZH2 to repress the EZH2-targeting microRNA miR-101,activating a switch,which stably upregulates EZH2.The cancer genome atlas(TCGA)data showing a correlation between KDM2B and EZH2 expression and Oncomine data,showing a correlation between KDM2B and tumor progression,strongly support the role of the FGF-2/KDM2B/miR-101/EZH2 pathway in bladder cancer.These observations combined,suggest a model according to which FGF-2 induces EMT,cell proliferation and cancer stem cell self-renewal by coupling the Akt3 and KDM2B-controlled pathways outlined above,in bladder carcinomas.Further analyses of publicly available databases,revealed that FGF-2-expressing bladder carcinomas carry fewer genetic alterations and they tend to express high levels of CTLA-4,PD-1 and PD-L1,which suggests immune blockade by checkpoint activation.EMT,enhanced proliferation and immune checkpoint activation combined,may be responsible for the poor prognosis of FGF-2-expressing bladder carcinomas. | Elizabeth A McNiel Philip N Tsichlis | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 6 |
| 2 | The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase显示文摘 | Thomas F Franke Sung-Il Yang Tung O Chan Ketaki Datta Andrius Kazlauskas Deborah K Morrison David R Kaplan Philip N Tsichlis | 1995 | Cell1995，，5： | 2 |
| 3 | Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor Growth and prolong remission 显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
| 4 | Oncogenic transformation induced by membrane - targeted Akt2 and Akt3 显示文摘 | Mende I Malstrom S Tsichlis PN | 2001 | Oneogene2001，20，32： | 1 |
| 5 | Akt/PKB and other D3 phosphoinositide-regulated kinases; Kinase activation by phosphoinositide-dependent phosphorylation显示文摘 | Chan TO Rittenhouse SE Tsichlis PN | 1999 | Annu Rev Biochem1999，68，： | 1 |
| 6 | Metformin selectively targets cancer stem cells,and acts together with chemotherapy to block tumor growth and prolong remission显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | | 0，，19： | 1 |
| 7 | Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
| 8 | AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1 显示文摘 | Corum DG Tsichlis PN Muise-Helmericks RC | 2014 | FASEB J2014，28，1： | 1 |
| 9 | Metformin selectively targets cancer stem cells,and acts together with chemotherapy to block tumor growth and prolong remission显示文摘 | Hirsch HA lliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
| 10 | Metformin selectively targets cancer stem cells,and acts together with chemotherapy to block tumor growth and prolong remission显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | | 0，，19： | 1 |
| 11 | Metformin selectively targets cancer stem cells,and acts together with chemotherapy to block tumor growth and prolong remission显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
| 12 | Metformin selective- ly targets cancer stem cells,and acts together with chemotherapy to block tumor growth and prolong remission显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
| 13 | The Akt-glycogen synthase kinase 3β pathway regulates transcription atrial natriuretic factor induced by β-adrenergic receptor stimulation in cardiac myocytes显示文摘 | Morisco C Zebroski D Condorelli G Tsichlis P Vatner SF Sadoshima J | 2000 | J Biol Chem2000，275，14： | 1 |
| 14 | Sequence comparison in the crossover region of an oncogenic avian retrovirus recombinant and its nononcogenic parent: genetic regions that control growth rate and oncogenic potential 显示文摘 | Tsichlis P N Donehower L Hager G | 1982 | Mol Cell Biol1982，2，11： | 1 |
| 15 | Recombinants be- tween endogenous and exogenous avian tumor viru- ses: role of the C region and other portions of the ge- nome in the control of replication and transformation 显示文摘 | TSICHLIS P N COFFIN J M | 1980 | J Virol1980，33，： | 1 |
| 16 | Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission 显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
| 17 | Metformin selectively targets cancer stem cells,and acts together with chemotherapy to block tumorgrowth and prolong remission 显示文摘 | HIRSCH H A ILIOPOULOS D TSICHLIS P N | 2009 | Cancer Research2009，69，19： | 1 |
| 18 | Akt signaling in normal and malignant cells 显示文摘 | Testa JR Tsichlis PN | 2005 | Oncogene2005，24，50： | 1 |
| 19 | Phosphoinositide 3-kinase signalling - which way to target显示文摘 | Chan TO Rittenhouse SE Tsichlis PN | | 0，，： | 1 |
| 20 | Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission 显示文摘 | Hirsch HA Iliopoulos D Tsichlis PN | 2009 | Cancer Res2009，69，19： | 1 |
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