Axl and Growth Arrest–Specific Gene 6 Are Frequently Overexpressed in Human Gliomas and Predict Poor Prognosis in Patients with Glioblastoma Multiforme

Hutterer, Markus; Knyazev, Pjotr; Abate, Ariane; Reschke, Markus; Maier, Hans; Stefanova, Nadia; Knyazeva, Tatjana; Barbieri, Verena; Reindl, Markus; Muigg, Armin; Kostron, Herwig; Stockhammer, Guenther; Ullrich, Axel

doi:10.1158/1078-0432.ccr-07-0862

Cited by 247 publications

(255 citation statements)

References 43 publications

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“…AXL is a member of the TAM (Tyro-3, AXL and Mer) family of receptor tyrosine kinases. AXL and its ligand, growth arrest-specific 6 are implicated in the pathogenesis of several human cancers including breast, lung, ovarian and prostate cancers and glioblastomas (Zhang et al, 2008;Shieh et al, 2005;Rankin et al, 2010;Sainaghi et al, 2005;Hutterer et al, 2008). AXL/growth arrest-specific 6 binding results in receptor dimerisation, tyrosine phosphorylation and activation of downstream pathways that regulate cytoskeletal dynamics/cell motility, cell survival and proliferation (reviewed in Linger et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL

et al. 2011

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Fos-related antigen 1 (Fra-1) is a Fos family member overexpressed in several types of human cancers. Here, we report that Fra-1 is highly expressed in the muscleinvasive form of the carcinoma of the bladder (80%) and to a lesser extent in superficial bladder cancer (42%). We demonstrate that in this type of cancer Fra-1 is regulated via a C-terminal instability signal and C-terminal phosphorylation. We show that manipulation of Fra-1 expression levels in bladder cancer cell lines affects cell morphology, motility and proliferation. The gene coding for AXL tyrosine kinase is directly upregulated by Fra-1 in bladder cancer and in other cell lines. Importantly, our data demonstrate that AXL mediates the effect of Fra-1 on tumour cell motility but not on cell proliferation. We suggest that AXL may represent an attractive therapeutic target in cancers expressing high Fra-1 levels.

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Section: Discussionmentioning

confidence: 99%

Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL

et al. 2011

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“…In the present study, we confirm that overexpression of MZF1 is tumorigenic, and for the first time, we report that MZF1 induces tumor growth and metastasis through the transactivation of Axl, thus adding to the molecular targets and mechanisms that can mediate an oncogenic potential of MZF1 in epithelialderived tissues. Axl has been reported as a transforming gene (21) that is overexpressed in several tumors (22)(23)(24)(25)(26)(27), and the Gas6/Axl signaling pathway is known to induce cell proliferation, antiapoptosis, migration, invasion, and angiogenic processes, which are most likely mediated through Ras, Src, mitogen-activated protein kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinase/Akt, and NF-κB signaling pathways (14,15,19,29,31,32,(44)(45)(46)(47)(48)(49). However, still further studies are needed to enhance the understanding of the downstream components of the Gas6/Axl signaling axis in tumor formation.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of Axl can transform fibroblasts even in the absence of a ligand (21), this is at least in part being mediated by Gas6/Axl-induced activation of mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase signaling. Following its identification in myeloid leukemia, Axl overexpression has been reported in several types of human solid cancers (22)(23)(24)(25)(26)(27). Axl expression correlates with poor prognosis in acute myeloid leukemia (28), gastric (29), and advanced lung adenocarcinoma patients (27), and with adhesion, motility, and invasiveness of osteosarcoma cells (30).…”

Section: Introductionmentioning

confidence: 99%

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Mudduluru

Vajkoczy

Allgayer

2010

Molecular Cancer Research

118

129

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Myeloid zinc finger 1 (MZF1) is a member of the SCAN domain family transcription factors that form dimers through their highly conserved SCAN motifs. Silencing of MZF1 inhibits cell proliferation, and abnormal expression of MZF1 results in cancer development. However, a potential role of MZF1 in metastasis remains unclear. Axl is a receptor tyrosine kinase and was first identified as a transforming gene in chronic myeloid leukemia. Axl overexpression induces proliferation, migration, and invasion and is highly expressed in different human cancers. In this study, we show that overexpression of MZF1 induces migration and invasion in colorectal (Rko, SW480) and cervical (HeLa) cancer cells. In addition, we show that MZF1 binds to the Axl promoter, transactivates promoter activity, and enhances Axl-mRNA and protein expression in a dose-dependent manner. In vitro, sh-RNA knockdown of Axl reduced MZF1-induced migration and invasion in HeLa and Rko cells (P = 0.05). Additionally, Rko cells overexpressing MZF1 showed increased tumor formation and liver metastasis in the chicken-embryo-metastasis assay in vivo. Furthermore, the expression of MZF1 and Axl was significantly higher in resected colorectal tumors compared with corresponding normal tissues (P = 0.02; P = 0.05), and MZF1 expression was positively correlated with Axl gene expression in tumor tissues (P < 0.01). Taken together, this is the first study to show that MZF1 induces invasion and in vivo metastasis in colorectal and cervical cancer, at least in part by regulating Axl gene expression. Mol Cancer Res; 8(2); 159-69. ©2010 AACR.

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“…Axl and PDGFRβ overexpression has been reported in several human cancers and associated with invasiveness and therapeutic resistance [27,28].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells

Esposito

Nuzzo

Kumar

et al. 2016

Journal of Controlled Release

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Release, 238 . pp. 43 57. ISSN 0168 3659 It is advisable to refer to the publisher's version if you intend to cite from the work.http://dx.doi.org/10. 1016/j.jconrel.2016.07.032 For more information about UCLan's research in this area go to http://www.uclan.ac.uk/researchgroups/ and search for . This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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Axl and Growth Arrest–Specific Gene 6 Are Frequently Overexpressed in Human Gliomas and Predict Poor Prognosis in Patients with Glioblastoma Multiforme

Cited by 247 publications

References 43 publications

Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL

Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells

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