zinc finger protein gli1


Summary: A transcriptional activator and oncogene protein that contains two CYS2-HIS2 ZINC FINGERS. Two isoforms are expressed; both regulate the expression of specific genes during development of craniofacial features, digits, the CENTRAL NERVOUS SYSTEM; and the GASTROINTESTINAL TRACT. They also regulate SONIC HEDGEHOG PROTEIN signaling and cell proliferation.

Top Publications

  1. Fernandez Zapico M. GLI1 finds a new role in cancer stem cell biology. EMBO Mol Med. 2013;5:483-5 pubmed publisher
  2. Colavito S, Zou M, Yan Q, Nguyen D, Stern D. Significance of glioma-associated oncogene homolog 1 (GLI1) expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Res. 2014;16:444 pubmed publisher
    ..Our results uncover crosstalk between NFκB and GLI1 signals and suggest that targeting these pathways may be effective against the claudin-low breast cancer subtype. ..
  3. Liu H, Yan S, Ding J, Yu T, Cheng S. DeSUMOylation of Gli1 by SENP1 Attenuates Sonic Hedgehog Signaling. Mol Cell Biol. 2017;37: pubmed publisher
  4. Lin Y, Huang Y, He J, Chen F, He Y, Zhang W. Role of Hedgehog-Gli1 signaling in the enhanced proliferation and differentiation of MG63 cells enabled by hierarchical micro-/nanotextured topography. Int J Nanomedicine. 2017;12:3267-3280 pubmed publisher
    ..These findings may aid in the optimization of hierarchical biomaterial topographies targeting Hedgehog-Gli1 signaling. ..
  5. Di Mauro C, Rosa R, D Amato V, Ciciola P, Servetto A, Marciano R, et al. Hedgehog signalling pathway orchestrates angiogenesis in triple-negative breast cancers. Br J Cancer. 2017;116:1425-1435 pubmed publisher
  6. Wu X, Zhang L, Toombs J, Kuo Y, Piazza J, Tuladhar R, et al. Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor. Nat Cell Biol. 2017;19:1226-1236 pubmed publisher
    ..Our findings delineate a chemical strategy for countering drug resistance in GLI-associated tumours and reveal unanticipated functions for BCL-2 proteins as transcriptional regulators. ..
  7. Neumann J, Wefers A, Lambo S, Bianchi E, Bockstaller M, Dorostkar M, et al. A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors. Nat Med. 2017;23:1191-1202 pubmed publisher
  8. Grajales Esquivel E, Luz Madrigal A, Bierly J, Haynes T, Reis E, Han Z, et al. Complement component C3aR constitutes a novel regulator for chick eye morphogenesis. Dev Biol. 2017;428:88-100 pubmed publisher
    ..Together our results show that C3aR is necessary for the proper morphogenesis of the OC. This is the first report implicating C3aR in eye development, revealing an unsuspected hitherto regulator for proper chick eye morphogenesis. ..
  9. Sena I, Prazeres P, Santos G, Borges I, Azevedo P, Andreotti J, et al. Identity of Gli1+ cells in the bone marrow. Exp Hematol. 2017;54:12-16 pubmed publisher
    ..This work introduces a new central cellular target for bone marrow fibrosis. The knowledge that emerges from this research will be important for the treatment of several malignant and nonmalignant disorders. ..

More Information


  1. Duan N, Liu X, Wu J. Palmitic acid elicits hepatic stellate cell activation through inflammasomes and hedgehog signaling. Life Sci. 2017;176:42-53 pubmed publisher
    ..Meanwhile, compromised autophagy may facilitate HSC activation, implicating valuable candidates for pharmacologic intervention against the progression of fibrogenesis in NASH. ..
  2. Ding J, Zhou X, Zou H, Wu J. Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug therapy through the ABCC1 transporter. Lab Invest. 2017;97:819-832 pubmed publisher
    ..Hedgehog signaling transcription factor Gli-2 appears to be the primary regulator for drug sensitivity of hepatoma through the ABCC1 transporter. ..
  3. Shao J, Gao Z, Huang W, Lu Z. The mechanism of epithelial-mesenchymal transition induced by TGF-?1 in neuroblastoma cells. Int J Oncol. 2017;50:1623-1633 pubmed publisher
    ..Specifically, EMT induced by TGF-?1 in neuroblastoma cells did not depend on the Smad signaling pathway, and the transcription factor Gli participated in TGF-?1-induced EMT independent of Smad signaling. ..
  4. Gunarta I, Li R, Nakazato R, Suzuki R, Boldbaatar J, Suzuki T, et al. Critical role of glioma-associated oncogene homolog 1 in maintaining invasive and mesenchymal-like properties of melanoma cells. Cancer Sci. 2017;108:1602-1611 pubmed publisher
    ..Our findings provide new insight into how heterogeneity and plasticity are achieved and regulated in melanoma. ..
  5. Ivina A, Semkin V, Babichenko I. [Immunohistochemical criteria for differential diagnostics of squamous epithelium changes in pyogenic granuloma and squamous cell carcinoma of the oral mucosa]. Stomatologiia (Mosk). 2017;96:33-35 pubmed publisher
    ..gli1 ?? ????????? ? ? ?????????? ??? ??????????????? ???????????? ????????????? ?????? ????????? ???????????????? ??? ???????????????. ..
  6. Moiseenko A, Kheirollahi V, Chao C, Ahmadvand N, Quantius J, Wilhelm J, et al. Origin and characterization of alpha smooth muscle actin-positive cells during murine lung development. Stem Cells. 2017;35:1566-1578 pubmed publisher
    ..5. Our results establish a new transcriptional landscape for further experiments addressing the function of signaling pathways in the formation of different subpopulations of ACTA2+ cells. Stem Cells 2017;35:1566-1578. ..
  7. Capurro M, Izumikawa T, Suarez P, Shi W, Cydzik M, Kaneiwa T, et al. Glypican-6 promotes the growth of developing long bones by stimulating Hedgehog signaling. J Cell Biol. 2017;216:2911-2926 pubmed publisher
    ..We conclude that GPC6 stimulates Hh signaling by binding to Hh and Ptc1 at the cilium and increasing the interaction of the receptor and ligand. ..
  8. Han Y, Xiong Y, Shi X, Wu J, Zhao Y, Jiang J. Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-?2 nuclear import system. PLoS Biol. 2017;15:e2002063 pubmed publisher
    ..Our study unravels the molecular mechanism and cellular machinery regulating Gli ciliary localization and identifies Kap?2 as a critical regulator of the Hh pathway and a potential drug target for Hh-driven cancers. ..
  9. Nayak A, Siddharth S, Das S, Nayak D, Sethy C, Kundu C. Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and ? catenin through activation of GSK3?. Toxicol Appl Pharmacol. 2017;330:53-64 pubmed publisher
    ..Thus, data suggest NQC caused OCSCs death by disrupting the crosstalk between ? catenin and GLI1 by activation of GSK3?. ..
  10. Alghamdi K, Alsaedi A, AlJasser A, Altawil A, Kamal N. Extended clinical features associated with novel Glis3 mutation: a case report. BMC Endocr Disord. 2017;17:14 pubmed publisher
    ..We suggest that infants with neonatal diabetes associated with dysmorphism should be screened for GLIS3 gene mutations. ..
  11. Ueda T, Tsubamoto H, Inoue K, Sakata K, Shibahara H, Sonoda T. Itraconazole Modulates Hedgehog, WNT/?-catenin, as well as Akt Signalling, and Inhibits Proliferation of Cervical Cancer Cells. Anticancer Res. 2017;37:3521-3526 pubmed
    ..Immunoblots showed suppression in ?-catenin expression and Akt phosphorylation. Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer. ..
  12. Feng J, Jing J, Li J, Zhao H, Punj V, Zhang T, et al. BMP signaling orchestrates a transcriptional network to control the fate of mesenchymal stem cells in mice. Development. 2017;144:2560-2569 pubmed publisher
  13. Zhang J, Zhao Y, Lv Y, Liu P, Ruan J, Sun Y, et al. miR-873 suppresses H9C2 cardiomyocyte proliferation by targeting GLI1. Gene. 2017;626:426-432 pubmed publisher
    ..To summarize, our data suggest that miR-873 is a novel miRNA that regulates H9C2 cell proliferation via targeting GLI1, and miR-873 may serve as a new potential biomarker diagnosis in CHD in the future. ..
  14. Onishi H, Nakamura K, Nagai S, Yanai K, Yamasaki A, Kawamoto M, et al. Hedgehog Inhibition Upregulates TRK Expression to Antagonize Tumor Suppression in Small Cell Lung Cancer Cells. Anticancer Res. 2017;37:4987-4992 pubmed
    ..These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC. ..
  15. Liu G, Huang W, Wang J, Liu X, Yang J, Zhang Y, et al. Discovery of Novel Macrocyclic Hedgehog Pathway Inhibitors Acting by Suppressing the Gli-Mediated Transcription. J Med Chem. 2017;60:8218-8245 pubmed publisher
  16. Ma Y, Yu W, Shrivastava A, Alemi F, Lankachandra K, Srivastava R, et al. Sanguinarine inhibits pancreatic cancer stem cell characteristics by inducing oxidative stress and suppressing sonic hedgehog-Gli-Nanog pathway. Carcinogenesis. 2017;38:1047-1056 pubmed publisher
    ..Our studies suggest that sanguinarine can be used for the treatment and/or prevention of pancreatic cancer by targeting CSCs. ..
  17. Chen S, Wang Y, Zhang W, Dong M, Zhang J. Sclareolide enhances gemcitabine?induced cell death through mediating the NICD and Gli1 pathways in gemcitabine?resistant human pancreatic cancer. Mol Med Rep. 2017;15:1461-1470 pubmed publisher
    ..Sclareolide may be a novel agent in combination with gemcitabine for the treatment of gemcitabine?resistant pancreatic cancer, which resensitizes GR?HPCCs to gemcitabine through mediating NICD and Gli1. ..
  18. Mahindroo N, Punchihewa C, Fujii N. Hedgehog-Gli signaling pathway inhibitors as anticancer agents. J Med Chem. 2009;52:3829-45 pubmed publisher
  19. Quintana A, Hernandez J, Gonzalez C. Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development. PLoS ONE. 2017;12:e0180856 pubmed publisher
    ..Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms. ..
  20. Pihlajoki M, Heikinheimo M, Wilson D. Never underestimate the complexity of remodeling. Endocrinology. 2013;154:4446-9 pubmed publisher
  21. Mierzwa A, Sullivan G, Beer L, Ahn S, Armstrong R. Comparison of cortical and white matter traumatic brain injury models reveals differential effects in the subventricular zone and divergent Sonic hedgehog signaling pathways in neuroblasts and oligodendrocyte progenitors. ASN Neuro. 2014;6: pubmed publisher
    ..Notably, cortical versus white matter damage from TBI produced opposite responses of Shh-activated cells within the SVZ. ..
  22. Ehe B, Lamson D, Tarpley M, Onyenwoke R, Graves L, Williams K. Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1. Biochem Biophys Res Commun. 2017;491:767-772 pubmed publisher
    ..The data described herein provide the first identification of a DYRK1A-mediated site of phosphorylation on GLI1 within its NLS and may serve as a valuable mechanism for further understanding Hh signaling modulation. ..
  23. Feng H, Lin J, Hsu S, Lan W, Kuo C, Tian Y, et al. Low folate metabolic stress reprograms DNA methylation-activated sonic hedgehog signaling to mediate cancer stem cell-like signatures and invasive tumour stage-specific malignancy of human colorectal cancers. Int J Cancer. 2017;141:2537-2550 pubmed publisher
    ..The study highlights CSC targets specific to LFMS-predisposed invasive CRC in optimizing folate co-chemotherapy to minimize tumour metastasis potential of CRC patients. ..
  24. Minami Y, Minami H, Miyamoto T, Yoshimoto G, Kobayashi Y, Munakata W, et al. Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies. Cancer Sci. 2017;108:1628-1633 pubmed publisher
    ..Glasdegib was safe and well tolerated across the dose levels tested. It is confirmed that the 100-mg dose is safe and tolerable in Japanese patients, and this dose level will be examined in the future clinical trial. ..
  25. Oladapo H, Tarpley M, Sauer S, Addo K, Ingram S, Strepay D, et al. Pharmacological targeting of GLI1 inhibits proliferation, tumor emboli formation and in vivo tumor growth of inflammatory breast cancer cells. Cancer Lett. 2017;411:136-149 pubmed publisher
    ..Our results indicated that GLI1 activation in TN-IBC as in TNBC, plays a vital role in promoting cell proliferation, motility, tumor growth, and formation of tumor emboli. ..
  26. Whisenant T, Ho D, Benz R, Rogers J, Kaake R, Gordon E, et al. Computational prediction and experimental verification of new MAP kinase docking sites and substrates including Gli transcription factors. PLoS Comput Biol. 2010;6: pubmed publisher
    ..These results demonstrate that a genome-wide search for MAP kinase docking sites can be used to find new docking sites and substrates. ..
  27. Dagklis A, Pauwels D, Lahortiga I, Geerdens E, Bittoun E, Cauwelier B, et al. Hedgehog pathway mutations in T-cell acute lymphoblastic leukemia. Haematologica. 2015;100:e102-5 pubmed publisher
  28. Long B, Wang L, Zheng F, Lai S, Xu D, Hu Y, et al. Targeting GLI1 Suppresses Cell Growth and Enhances Chemosensitivity in CD34+ Enriched Acute Myeloid Leukemia Progenitor Cells. Cell Physiol Biochem. 2016;38:1288-302 pubmed publisher
    ..The present findings suggested that Hh signaling was activated in AML progenitor cells. GLI1 acted as a potential target for AML therapy. ..
  29. Cui Y, Cui C, Yang Z, Ni W, Jin Y, Xuan Y. Gli1 expression in cancer stem-like cells predicts poor prognosis in patients with lung squamous cell carcinoma. Exp Mol Pathol. 2017;102:347-353 pubmed publisher
    ..026). Our results suggest that Gli1 may be a potential LSCC stem cell marker and an independent indicator of poor prognosis for patients with LSCC. ..
  30. Yang Z, Lv Y, Wang L, Chen Y, Han J, Zhao S, et al. Inhibition of hedgehog pathway reveals the regulatory role of SMO in gastric cancer cells. Tumour Biol. 2017;39:1010428317715546 pubmed publisher
    ..Our studies demonstrate an important role for smoothened and glioma-associated oncogene homology-1 in gastric cancer and suggest inhibition of hedgehog pathway as a novel and potent strategy to treat gastric cancer patients. ..
  31. Liang M, Yu M, Xia R, Song K, Wang J, Luo J, et al. Yap/Taz Deletion in Gli+ Cell-Derived Myofibroblasts Attenuates Fibrosis. J Am Soc Nephrol. 2017;28:3278-3290 pubmed publisher
    ..Identifying mechanisms that interrupt this profibrotic cycle could lead to the development of anti-fibrosis therapy. ..
  32. Wadhwa R, Wang X, Baladandayuthapani V, Liu B, Shiozaki H, Shimodaira Y, et al. Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients. Br J Cancer. 2017;117:648-655 pubmed publisher
    ..Our validated data in OC show that nuclear Gli-1 LIs are predictive of pathCR after chemoradiation with desirable sensitivity and specificity. ..
  33. Ming J, Sun B, Li Z, Lin L, Meng X, Han B, et al. Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy. Aging (Albany NY). 2017;9:1233-1247 pubmed publisher
    ..Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma. ..
  34. Ni W, Yang Z, Qi W, Cui C, Cui Y, Xuan Y. Gli1 is a potential cancer stem cell marker and predicts poor prognosis in ductal breast carcinoma. Hum Pathol. 2017;69:38-45 pubmed publisher
    ..038). Moreover, Gli1 expression correlated significantly with the expression of two CSC markers, Sox2 (P=.01) and LSD1 (P=.01). Gli1 could be a stem cell marker and an indicator of poor prognosis in patients with ductal breast carcinoma. ..
  35. Kasiri S, Shao C, Chen B, Wilson A, Yenerall P, Timmons B, et al. GLI1 Blockade Potentiates the Antitumor Activity of PI3K Antagonists in Lung Squamous Cell Carcinoma. Cancer Res. 2017;77:4448-4459 pubmed publisher
    ..i>Cancer Res; 77(16); 4448-59. ©2017 AACR. ..