Inhibition of GSK‐3β activity attenuates proliferation of human colon cancer cells in rodents

Shakoori, Abbas; Mai, Wei; Miyashita, Katsuyoshi; Yasumoto, Keiichi; Takahashi, Yutaka; Ooi, Akishi; Kawakami, Kazuyuki; Minamoto, Toshinari

doi:10.1111/j.1349-7006.2007.00545.x

Cited by 127 publications

(138 citation statements)

References 47 publications

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“…6A). Similar to our previous studies (19,25), no detrimental effects were observed in mice treated with GSK3b inhibitor. There was no significant difference in body weight between groups treated with DMSO and AR-A014418.…”

Section: Changes In the Invasive Phenotype Following Gsk3b Inhibitionsupporting

confidence: 90%

“…Histologically, the tumors showed dense palisades of tumor cells around areas of necrosis, the presence of bizarre giant cells and the proliferation of microvasculature, all of which are characteristic of human glioblastoma (1). The 12 mice were treated by intraperitoneal injection of either DMSO (n ¼ 6) or AR-A014418 (2 mg/kg body weight; n ¼ 6) three times a week, as described earlier (19,25). All mice were euthanized at the end of 2 weeks of treatment.…”

Section: Animal Study Immunohistochemical and Biochemical Analysismentioning

confidence: 99%

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Glycogen Synthase Kinase 3β Sustains Invasion of Glioblastoma via the Focal Adhesion Kinase, Rac1, and c-Jun N-Terminal Kinase-Mediated Pathway

Chikano

Domoto

Furuta

et al. 2015

Molecular Cancer Therapeutics

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The failure of current treatment options for glioblastoma stems from their inability to control tumor cell proliferation and invasion. Biologically targeted therapies offer great hope and one promising target is glycogen synthase kinase-3b (GSK3b), implicated in various diseases, including cancer. We previously reported that inhibition of GSK3b compromises the survival and proliferation of glioblastoma cells, induces their apoptosis, and sensitizes them to temozolomide and radiation. Here, we explore whether GSK3b also contributes to the highly invasive nature of glioblastoma. The effects of GSK3b inhibition on migration and invasion of glioblastoma cells were examined by wound-healing and Transwell assays, as well as in a mouse model of glioblastoma. We also investigated changes in cellular microarchitectures, cytoskeletal components, and proteins responsible for cell motility and invasion. Inhibition of GSK3b attenuated the migration and invasion of glioblastoma cells in vitro and that of tumor cells in a mouse model of glioblastoma. These effects were associated with suppression of the molecular axis involving focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase. Changes in cellular phenotypes responsible for cell motility and invasion were also observed, including decreased formation of lamellipodia and invadopodium-like microstructures and alterations in the subcellular localization, and activity of Rac1 and F-actin. These changes coincided with decreased expression of matrix metalloproteinases. Our results confirm the potential of GSK3b as an attractive therapeutic target against glioblastoma invasion, thus highlighting a second role in this tumor type in addition to its involvement in chemo-and radioresistance. Mol Cancer Ther; 14(2); 564-74. Ó2014 AACR.

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Section: Changes In the Invasive Phenotype Following Gsk3b Inhibitionsupporting

confidence: 90%

Section: Animal Study Immunohistochemical and Biochemical Analysismentioning

confidence: 99%

Glycogen Synthase Kinase 3β Sustains Invasion of Glioblastoma via the Focal Adhesion Kinase, Rac1, and c-Jun N-Terminal Kinase-Mediated Pathway

Chikano

Domoto

Furuta

et al. 2015

Molecular Cancer Therapeutics

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“…More recent studies indicate a role for GSK3 in the control of neoplastic transformation and tumor development (reviewd in Miyashita et al, 2009b). Overexpression and activation of GSK3 was confirmed in various kinds of cancers such as colorectal, stomach, pancreatic, and liver cancers, as well as leukemia and GBM (Shakoori et al, 2005;Shakoori et al, 2007;Wang et al, 2008;Miyashita et al, 2009a;Mai et al, 2009). Previous studies have shown that inhibition of GSK3 suppresses cancer cell proliferation and induces apoptosis Ougolkov et al, 2007).…”

Section: Pathological Functionmentioning

confidence: 97%

The Pivotal Roles of GSK3β in Glioma Biology

Nakada¹,

Minamoto²,

Pyko³

et al. 2011

Molecular Targets of CNS Tumors

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“…MLL-rearranged leukemic cells are dependent on GSK3, as GSK3 inhibitors induce proliferation arrest in these cells. 112 Inhibition of GSK3 with lithium already showed potential in these studies, but further research is warranted as GSK3 slows other malignancies, for example, colon cancer, 113 and induces chromosomal instability. 114 RAS pathway signaling has a significant role in leukemogenesis in AML.…”

Section: Toward Targeted Therapymentioning

confidence: 99%

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

et al. 2011

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Translocations involving the mixed-lineage leukemia (MLL) gene, localized at 11q23, comprise 15 to 20% of all pediatric acute myeloid leukemia (AML) cases. This review summarizes current knowledge about the etiology, biology, clinical characteristics and differences in outcome in MLL-rearranged pediatric AML. Furthermore, we discuss the role of cooperating events in MLL-rearranged pediatric AML, and future therapeutic strategies to improve outcome. We conclude that MLL-rearranged pediatric AML is a heterogeneous disease, and prognosis depends on various factors, for example, translocation partner, age, WBC and additional cytogenetic aberrations. The relationship of outcome with specific translocation partners requires that they be searched for in the diagnostic work-up of AML. To achieve further improvements in outcome, unraveling the biology of MLL-rearranged pediatric AML is warranted.

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Inhibition of GSK‐3β activity attenuates proliferation of human colon cancer cells in rodents

Abstract: The authors' recent discovery that glycogen synthase kinase-3β β β β (GSK-3β β β β) participates in colon cancer cells' survival and proliferation prompted us to investigate whether GSK-3β β β β inhibition alters proliferation of colon cancer cells in vivo.

Cited by 127 publications

References 47 publications

Glycogen Synthase Kinase 3β Sustains Invasion of Glioblastoma via the Focal Adhesion Kinase, Rac1, and c-Jun N-Terminal Kinase-Mediated Pathway

Glycogen Synthase Kinase 3β Sustains Invasion of Glioblastoma via the Focal Adhesion Kinase, Rac1, and c-Jun N-Terminal Kinase-Mediated Pathway

The Pivotal Roles of GSK3β in Glioma Biology

The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia

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