Skip to main content
Erschienen in: Journal of Neuro-Oncology 1/2015

01.10.2015 | Laboratory Investigation

Hugl-1 inhibits glioma cell growth in intracranial model

verfasst von: Xuejiao Liu, Dong Lu, Peng Ma, Huaqiang Liu, Yuewen Cao, Ben Sang, Xianlong Zhu, Qiong Shi, Jinxia Hu, Rutong Yu, Xiuping Zhou

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Drosophila lethal (2) giant larvae (lgl) has been reported as a tumor suppressor and could regulate the Drosophila hippo signaling. Human giant larvae-1(Hugl-1), one human homologue of Drosophila lgl, also has been reported to be involved in the development of some human cancers. However, whether Hugl-1 is associated with the pathogenesis of malignant gliomas remains poorly understood. In the present work, we examined the effect of Hugl-1 on glioma cell growth both in vitro and in vivo. Firstly, we found that Hugl-1 protein levels decreased in the human glioma tissues, suggesting that Hugl-1 is involved in glioma progression. Unfortunately, either stably or transiently over-expressing Hugl-1 did not affect glioma cell proliferation in vitro. In addition, Hugl-1 over-expression did not regulate hippo signaling pathway. Interestingly, over-expression of Hugl-1 not only inhibited gliomagenesis but also markedly inhibited cell proliferation and promoted the apoptosis of U251 cells in an orthotopic model of nude mice. Taken together, this study provides the evidence that Hugl-1 inhibits glioma cell growth in intracranial model of nude mice, suggesting that Hugl-1 might be a potential tumor target for glioma therapy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY (2012) Primary brain tumours in adults. Lancet 379(9830):1984–1996CrossRefPubMed Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY (2012) Primary brain tumours in adults. Lancet 379(9830):1984–1996CrossRefPubMed
2.
Zurück zum Zitat Oike T, Suzuki Y, Sugawara K, Shirai K, Noda SE, Tamaki T, Nagaishi M, Yokoo H, Nakazato Y, Nakano T (2013) Radiotherapy plus concomitant adjuvant temozolomide for glioblastoma: Japanese mono-institutional results. PLoS ONE 8(11):e78943PubMedCentralCrossRefPubMed Oike T, Suzuki Y, Sugawara K, Shirai K, Noda SE, Tamaki T, Nagaishi M, Yokoo H, Nakazato Y, Nakano T (2013) Radiotherapy plus concomitant adjuvant temozolomide for glioblastoma: Japanese mono-institutional results. PLoS ONE 8(11):e78943PubMedCentralCrossRefPubMed
3.
Zurück zum Zitat Schmidt NO, Ziu M, Carrabba G, Giussani C, Bello L, Sun Y, Schmidt K, Albert M, Black PM, Carroll RS (2004) Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma model. Clin Cancer Res 10(4):1255–1262CrossRefPubMed Schmidt NO, Ziu M, Carrabba G, Giussani C, Bello L, Sun Y, Schmidt K, Albert M, Black PM, Carroll RS (2004) Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma model. Clin Cancer Res 10(4):1255–1262CrossRefPubMed
5.
Zurück zum Zitat Grifoni D, Garoia F, Bellosta P, Parisi F, De Biase D, Collina G, Strand D, Cavicchi S, Pession A (2007) aPKCζ cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia. Oncogene 26(40):5960–5965CrossRefPubMed Grifoni D, Garoia F, Bellosta P, Parisi F, De Biase D, Collina G, Strand D, Cavicchi S, Pession A (2007) aPKCζ cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia. Oncogene 26(40):5960–5965CrossRefPubMed
6.
Zurück zum Zitat Ohshiro T, Yagami T, Zhang C, Matsuzaki F (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408(6812):593–596CrossRefPubMed Ohshiro T, Yagami T, Zhang C, Matsuzaki F (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408(6812):593–596CrossRefPubMed
7.
Zurück zum Zitat Strand D, Jakobs R, Merdes G, Neumann B, Kalmes A, Heid HW, Husmann I, Mechler BM (1994) The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. J Cell Biol 127(5):1361–1373CrossRefPubMed Strand D, Jakobs R, Merdes G, Neumann B, Kalmes A, Heid HW, Husmann I, Mechler BM (1994) The Drosophila lethal(2)giant larvae tumor suppressor protein forms homo-oligomers and is associated with nonmuscle myosin II heavy chain. J Cell Biol 127(5):1361–1373CrossRefPubMed
8.
Zurück zum Zitat Strand D, Raska I, Mechler BM (1994) The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton. J Cell Biol 127(5):1345–1360CrossRefPubMed Strand D, Raska I, Mechler BM (1994) The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton. J Cell Biol 127(5):1345–1360CrossRefPubMed
9.
Zurück zum Zitat Froldi F, Ziosi M, Tomba G, Parisi F, Garoia F, Pession A, Grifoni D (2008) Drosophila lethal giant larvae neoplastic mutant as a genetic tool for cancer modeling. Curr Genomics 9(3):147–154PubMedCentralCrossRefPubMed Froldi F, Ziosi M, Tomba G, Parisi F, Garoia F, Pession A, Grifoni D (2008) Drosophila lethal giant larvae neoplastic mutant as a genetic tool for cancer modeling. Curr Genomics 9(3):147–154PubMedCentralCrossRefPubMed
10.
Zurück zum Zitat Grzeschik NA, Parsons LM, Allott ML, Harvey KF, Richardson HE (2010) Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol 20(7):573–581CrossRefPubMed Grzeschik NA, Parsons LM, Allott ML, Harvey KF, Richardson HE (2010) Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol 20(7):573–581CrossRefPubMed
11.
Zurück zum Zitat Rolls MM, Albertson R, Shih HP, Lee CY, Doe CQ (2003) Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol 163(5):1089–1098PubMedCentralCrossRefPubMed Rolls MM, Albertson R, Shih HP, Lee CY, Doe CQ (2003) Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol 163(5):1089–1098PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Zimmermann T, Kashyap A, Hartmann U, Otto G, Galle PR, Strand S, Strand D (2008) Cloning and characterization of the promoter of Hugl-2, the human homologue of Drosophila lethal giant larvae (lgl) polarity gene. Biochem Biophys Res Commun 366(4):1067–1073CrossRefPubMed Zimmermann T, Kashyap A, Hartmann U, Otto G, Galle PR, Strand S, Strand D (2008) Cloning and characterization of the promoter of Hugl-2, the human homologue of Drosophila lethal giant larvae (lgl) polarity gene. Biochem Biophys Res Commun 366(4):1067–1073CrossRefPubMed
13.
Zurück zum Zitat Strand D, Unger S, Corvi R, Hartenstein K, Schenkel H, Kalmes A, Merdes G, Neumann B, Krieg-Schneider F, Coy JF et al (1995) A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain. Oncogene 11(2):291–301PubMed Strand D, Unger S, Corvi R, Hartenstein K, Schenkel H, Kalmes A, Merdes G, Neumann B, Krieg-Schneider F, Coy JF et al (1995) A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain. Oncogene 11(2):291–301PubMed
14.
Zurück zum Zitat Grifoni D, Garoia F, Schimanski CC, Schmitz G, Laurenti E, Galle PR, Pession A, Cavicchi S, Strand D (2004) The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour suppressor function in vivo. Oncogene 23(53):8688–8694CrossRefPubMed Grifoni D, Garoia F, Schimanski CC, Schmitz G, Laurenti E, Galle PR, Pession A, Cavicchi S, Strand D (2004) The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour suppressor function in vivo. Oncogene 23(53):8688–8694CrossRefPubMed
15.
Zurück zum Zitat Schimanski CC, Schmitz G, Kashyap A, Bosserhoff AK, Bataille F, Schafer SC, Lehr HA, Berger MR, Galle PR, Strand S, Strand D (2005) Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Oncogene 24(19):3100–3109CrossRefPubMed Schimanski CC, Schmitz G, Kashyap A, Bosserhoff AK, Bataille F, Schafer SC, Lehr HA, Berger MR, Galle PR, Strand S, Strand D (2005) Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Oncogene 24(19):3100–3109CrossRefPubMed
16.
Zurück zum Zitat Kuphal S, Wallner S, Schimanski CC, Bataille F, Hofer P, Strand S, Strand D, Bosserhoff AK (2006) Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25(1):103–110PubMed Kuphal S, Wallner S, Schimanski CC, Bataille F, Hofer P, Strand S, Strand D, Bosserhoff AK (2006) Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25(1):103–110PubMed
17.
Zurück zum Zitat Lu XF, Feng XJ, Man XB, Yang G, Tang L, Du D, Zhang F, Yuan HX, Huang Q, Zhang Z, Liu YK, Strand D, Chen ZJ (2009) Aberrant splicing of Hugl-1 is associated with hepatocellular carcinoma progression. Clin Cancer Res 15(10):3287–3296CrossRefPubMed Lu XF, Feng XJ, Man XB, Yang G, Tang L, Du D, Zhang F, Yuan HX, Huang Q, Zhang Z, Liu YK, Strand D, Chen ZJ (2009) Aberrant splicing of Hugl-1 is associated with hepatocellular carcinoma progression. Clin Cancer Res 15(10):3287–3296CrossRefPubMed
18.
Zurück zum Zitat Biesterfeld S, Kauhausen A, Kost C, Gockel I, Schimanski CC, Galle PR (2012) Preservation of HUGL-1 expression as a favourable prognostic factor in pancreatic carcinoma. Anticancer Res 32(8):3153–3159PubMed Biesterfeld S, Kauhausen A, Kost C, Gockel I, Schimanski CC, Galle PR (2012) Preservation of HUGL-1 expression as a favourable prognostic factor in pancreatic carcinoma. Anticancer Res 32(8):3153–3159PubMed
19.
Zurück zum Zitat Song J, Peng XL, Ji MY, Ai MH, Zhang JX, Dong WG (2013) Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo. World J Gastroenterol 19(26):4127–4136PubMedCentralCrossRefPubMed Song J, Peng XL, Ji MY, Ai MH, Zhang JX, Dong WG (2013) Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo. World J Gastroenterol 19(26):4127–4136PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Wang T, Liu Y, Xu XH, Deng CY, Wu KY, Zhu J, Fu XQ, He M, Luo ZG (2011) Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal polarization. Dev Cell 21(3):431–444CrossRefPubMed Wang T, Liu Y, Xu XH, Deng CY, Wu KY, Zhu J, Fu XQ, He M, Luo ZG (2011) Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal polarization. Dev Cell 21(3):431–444CrossRefPubMed
21.
Zurück zum Zitat Zhou X, Meng Q, Xu X, Zhi T, Shi Q, Wang Y, Yu R (2012) Bex2 regulates cell proliferation and apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway. Biochem Biophys Res Commun 427(3):574–580CrossRefPubMed Zhou X, Meng Q, Xu X, Zhi T, Shi Q, Wang Y, Yu R (2012) Bex2 regulates cell proliferation and apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway. Biochem Biophys Res Commun 427(3):574–580CrossRefPubMed
22.
Zurück zum Zitat Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK, Alvarez-Buylla A, Parada LF (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15(1):45–56PubMedCentralCrossRefPubMed Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK, Alvarez-Buylla A, Parada LF (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15(1):45–56PubMedCentralCrossRefPubMed
23.
Zurück zum Zitat Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA (2001) Malignant glioma: genetics and biology of a grave matter. Genes Dev 15(11):1311–1333CrossRefPubMed Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA (2001) Malignant glioma: genetics and biology of a grave matter. Genes Dev 15(11):1311–1333CrossRefPubMed
24.
25.
Zurück zum Zitat Tsuruga T, Nakagawa S, Watanabe M, Takizawa S, Matsumoto Y, Nagasaka K, Sone K, Hiraike H, Miyamoto Y, Hiraike O, Minaguchi T, Oda K, Yasugi T, Yano T, Taketani Y (2007) Loss of Hugl-1 expression associates with lymph node metastasis in endometrial cancer. Oncol Res 16(9):431–435PubMed Tsuruga T, Nakagawa S, Watanabe M, Takizawa S, Matsumoto Y, Nagasaka K, Sone K, Hiraike H, Miyamoto Y, Hiraike O, Minaguchi T, Oda K, Yasugi T, Yano T, Taketani Y (2007) Loss of Hugl-1 expression associates with lymph node metastasis in endometrial cancer. Oncol Res 16(9):431–435PubMed
26.
Zurück zum Zitat Tsuruga T, Nakagawa S, Watanabe M, Takizawa S, Matsumoto Y, Nagasaka K, Sone K, Hiraike H, Miyamoto Y, Hiraike O, Minaguchi T, Oda K, Yasugi T, Yano T, Taketani Y (2007) Loss of Hugl-1 expression associates with lymph node metastasis in endometrial cancer. Oncol Res 16(9):431–435PubMed Tsuruga T, Nakagawa S, Watanabe M, Takizawa S, Matsumoto Y, Nagasaka K, Sone K, Hiraike H, Miyamoto Y, Hiraike O, Minaguchi T, Oda K, Yasugi T, Yano T, Taketani Y (2007) Loss of Hugl-1 expression associates with lymph node metastasis in endometrial cancer. Oncol Res 16(9):431–435PubMed
27.
Zurück zum Zitat Kuphal S, Wallner S, Schimanski CC, Bataille F, Hofer P, Strand S, Strand D, Bosserhoff AK (2006) Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25(1):103–110PubMed Kuphal S, Wallner S, Schimanski CC, Bataille F, Hofer P, Strand S, Strand D, Bosserhoff AK (2006) Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25(1):103–110PubMed
28.
29.
Zurück zum Zitat Ware ML, Berger MS, Binder DK (2003) Molecular biology of glioma tumorigenesis. Histol Histopathol 18(1):207–216PubMed Ware ML, Berger MS, Binder DK (2003) Molecular biology of glioma tumorigenesis. Histol Histopathol 18(1):207–216PubMed
30.
Zurück zum Zitat Auvergne RM, Sim FJ, Wang S, Chandler-Militello D, Burch J, Al Fanek Y, Davis D, Benraiss A, Walter K, Achanta P, Johnson M, Quinones-Hinojosa A, Natesan S, Ford HL, Goldman SA (2013) Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes. Cell Rep 3(6):2127–2141CrossRefPubMed Auvergne RM, Sim FJ, Wang S, Chandler-Militello D, Burch J, Al Fanek Y, Davis D, Benraiss A, Walter K, Achanta P, Johnson M, Quinones-Hinojosa A, Natesan S, Ford HL, Goldman SA (2013) Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes. Cell Rep 3(6):2127–2141CrossRefPubMed
31.
Zurück zum Zitat Milinkovic V, Bankovic J, Rakic M, Stankovic T, Skender-Gazibara M, Ruzdijic S, Tanic N (2013) Identification of novel genetic alterations in samples of malignant glioma patients. PLoS ONE 8(12):e82108PubMedCentralCrossRefPubMed Milinkovic V, Bankovic J, Rakic M, Stankovic T, Skender-Gazibara M, Ruzdijic S, Tanic N (2013) Identification of novel genetic alterations in samples of malignant glioma patients. PLoS ONE 8(12):e82108PubMedCentralCrossRefPubMed
32.
Zurück zum Zitat Swartz MA, Iida N, Roberts EW, Sangaletti S, Wong MH, Yull FE, Coussens LM, DeClerck YA (2012) Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res 72(10):2473–2480PubMedCentralCrossRefPubMed Swartz MA, Iida N, Roberts EW, Sangaletti S, Wong MH, Yull FE, Coussens LM, DeClerck YA (2012) Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res 72(10):2473–2480PubMedCentralCrossRefPubMed
33.
36.
Zurück zum Zitat Chan SW, Lim CJ, Chen L, Chong YF, Huang C, Song H, Hong W (2011) The Hippo pathway in biological control and cancer development. J Cell Physiol 226(4):928–939CrossRefPubMed Chan SW, Lim CJ, Chen L, Chong YF, Huang C, Song H, Hong W (2011) The Hippo pathway in biological control and cancer development. J Cell Physiol 226(4):928–939CrossRefPubMed
37.
Zurück zum Zitat Konsavage WM, Kyler SL, Rennoll SA, Jin G, Yochum GS (2012) Wnt/beta-catenin signaling regulates yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem 287(15):11730–11739PubMedCentralCrossRefPubMed Konsavage WM, Kyler SL, Rennoll SA, Jin G, Yochum GS (2012) Wnt/beta-catenin signaling regulates yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem 287(15):11730–11739PubMedCentralCrossRefPubMed
38.
Zurück zum Zitat Fernandez A, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, Taylor MD, Kenney AM (2009) YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev 23(23):2729–2741CrossRef Fernandez A, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, Taylor MD, Kenney AM (2009) YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev 23(23):2729–2741CrossRef
Metadaten
Titel
Hugl-1 inhibits glioma cell growth in intracranial model
verfasst von
Xuejiao Liu
Dong Lu
Peng Ma
Huaqiang Liu
Yuewen Cao
Ben Sang
Xianlong Zhu
Qiong Shi
Jinxia Hu
Rutong Yu
Xiuping Zhou
Publikationsdatum
01.10.2015
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2015
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1901-3

Weitere Artikel der Ausgabe 1/2015

Journal of Neuro-Oncology 1/2015 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.