nach oben

Tumor Biology

Erschienen in:

23.09.2016 | Original Article

Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance

verfasst von: M. H. Shahi, S. Farheen, M. P. M. Mariyath, J. S. Castresana

Erschienen in: Tumor Biology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments. GANT61 very efficiently inhibited cell colony growth in glioma cell lines, compared to temozolomide. Moreover, a synergic effect of GANT61 and temozolomide drastically decreased the LD50 of temozolomide in the cell colony experiments. Therefore, our results suggest that there is a potential nexus of Shh-Gli1-BMI1 cell signaling to regulate MRP1 and to promote chemoresistance in glioma. Henceforth, our study opens the possibility of facing new targets, Gli1 and BMI1, for the effective treatment of glioma suppression of chemoresistance with adjuvant therapy of GANT61 and temozolomide.

Lasky JL, Choe M, Nakano I. Cancer stem cells in pediatric brain tumors. Curr Stem Cell Res Ther. 2009;4:298–305.CrossRefPubMed

Dahmane N, Ruiz i Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development. 1999;126:3089–100.PubMed

Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 2007;17:165–72.CrossRefPubMed

Schiapparelli P, Shahi MH, Enguita-German M, Johnsen JI, Kogner P, Lazcoz P, et al. Inhibition of the sonic hedgehog pathway by cyplopamine reduces the CD133+/CD15+ cell compartment and the in vitro tumorigenic capability of neuroblastoma cells. Cancer Lett. 2011;310:222–31.CrossRefPubMed

Shahi MH, Lorente A, Castresana JS. Hedgehog signaling in medulloblastoma, glioblastoma and neuroblastoma. Oncol Rep. 2008;19:681–8.PubMed

Shahi MH, Schiapparelli P, Afzal M, Sinha S, Rey JA, Castresana JS. Expression and epigenetic modulation of sonic hedgehog-GLI1 pathway genes in neuroblastoma cell lines and tumors. Tumor Biol. 2011;32:113–27.CrossRef

Yoon JW, Kita Y, Frank DJ, Majewski RR, Konicek BA, Nobrega MA, et al. Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J Biol Chem. 2002;277:5548–55.CrossRefPubMed

Leung C, Lingbeek M, Shakhova O, Liu J, Tanger E, Saremaslani P, et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature. 2004;428:337–41.CrossRefPubMed

van Lohuizen M, Verbeek S, Scheljen B, Wientjens E, van der Guidon H, Berns A. Identification of cooperating oncogenes in Eμ-myc transgenic mice by provirus tagging. Cell. 1991;65:737–52.CrossRefPubMed

10.

Facchino S, Abdouh M, Chatoo W, Bernier G. BMI1 confers radioresistance to normal and cancerous neural stem cells through recruitment of the DNA damage response machinery. J Neurosci. 2010;30:10096–111.CrossRefPubMed

11.

Natsume A, Kinjo S, Yuki K, Kato T, Ohno M, Motomura K, et al. Glioma-initiating cells and molecular pathology: implications for therapy. Brain Tumor Pathol. 2011;28:1–12.CrossRefPubMed

12.

Subkhankulova T, Zhang X, Leung C, Marino S. Bmi1 directly represses p21Waf1/Cip1 in Shh-induced proliferation of cerebellar granule cell progenitors. Mol Cell Neurosci. 2010;45:151–62.CrossRefPubMed

13.

Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003;100:15178–83.CrossRefPubMedPubMedCentral

14.

He S, Nakada D, Morrison SJ. Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol. 2009;25:377–406.CrossRefPubMed

15.

Yadirgi G, Leinster V, Acquati S, Bhagat H, Shakhova O, Marino S. Conditional activation of Bmi1 expression regulates self-renewal, apoptosis, and differentiation of neural stem/progenitor cells in vitro and in vivo. Stem Cells. 2011;29:700–12.CrossRefPubMed

16.

Häyry V, Tynninen O, Haapasalo HK, Wölfer J, Paulus W, Hasselblatt M, et al. Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumors. Neuropathol Appl Neurobiol. 2008;34:555–63.CrossRefPubMed

17.

Bruggeman SWM, Hulsman D, Tanger E, Buckle T, Blom M, Zevenhoven J, et al. Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell. 2007;12:328–41.CrossRefPubMed

18.

Xia H, Cheung WKC, Ng SS, Jiang X, Jiang S, Sze J, et al. Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells. J Biol Chem. 2012;287:9962–71.CrossRefPubMedPubMedCentral

19.

Barisone GA, Ngo T, Tran M, Cortes D, Shahi MH, Nguyen TV, et al. Role of MXD3 in proliferation of DAOY human medulloblastoma cells. PLoS One. 2012;7.

20.

Shahi MH, Afzal M, Sinha S, Eberhart CG, Rey JA, Fan X, et al. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, cyclin D2, plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma. BMC Cancer. 2010;10:614.CrossRefPubMedPubMedCentral

21.

Shahi MH, Holt R, Rebhun, RB. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells. PLoS One. 2014;9.

22.

Shahi MH, York D, Gandour-Edwards R, Withers SS, Holt R, Rebhun RB. BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance. PLoS One. 2015;10:1–17.CrossRef

23.

Garrido W, Rocha JD, Jaramillo C, Fernandez K, Oyarzun C, San Martin R, et al. Chemoresistance in high-grade gliomas: relevance of adenosine signaling in stem-like cells of glioblastoma multiforme. Curr Drug Targets. 2014;15:931–42.PubMed

24.

Tivnan A, Zakaria Z, O’Leary C, Kögel D, Pokorny JL, Sarkaria JN, et al.. Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme. Front Neurosci. 2015;9.

25.

Calatozzolo C, Gelati M, Ciusani E, Sciacca FL, Pollo B, Cajola L, et al. Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neuro-Oncol. 2005;74:113–21.CrossRef

26.

Spiegl-Kreinecker S, Buchroithner J, Elbling L, Steiner E, Wurm G, Bodenteich A, et al. Expression and functional activity of the ABC-transporter proteins P-glycoprotein and multidrug-resistance protein 1 in human brain tumor cells and astrocytes. J Neuro-Oncol. 2002;57:27–36.CrossRef

27.

Wang X, Venugopal C, Manoranjan B, McFarlane N, O’Farrell E, Nolte S, et al. Sonic hedgehog regulates Bmi1 in human medulloblastoma brain tumor-initiating cells. Oncogene. 2011:187–99.

Titel: Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance
verfasst von: M. H. Shahi
S. Farheen
M. P. M. Mariyath
J. S. Castresana
Publikationsdatum: 23.09.2016
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 11/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-5365-7

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2016

Direct targeting of HGF by miR-16 regulates proliferation and migration in gastric cancer

Antiproliferative and apoptotic effects of a specific anti-insulin-like growth factor I receptor single chain antibody on breast cancer cells

Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells

Targeting Netrin-1 in glioblastoma stem-like cells inhibits growth, invasion, and angiogenesis

Arsenic trioxide inhibits lung metastasis of mouse colon cancer via reducing the infiltration of regulatory T cells

Epigenetic regulation of human retinoblastoma

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie