Protein 4.1B/Differentially Expressed in Adenocarcinoma of the Lung-1 Functions as a Growth Suppressor in Meningioma Cells by Activating Rac1-Dependent c-Jun-NH2-kinase Signaling

Gerber, Mark A.; Bahr, Scott M.; Gutmann, David H.

doi:10.1158/0008-5472.can-05-1628

Cited by 35 publications

(35 citation statements)

References 51 publications

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“…DAL-1 forms a functional complex with CASPR2. This complex is thought to be involved in cell signaling through the activation of c-Jun amino-terminal kinase, a regulator of the retinoblastoma protein (Gerber et al, 2006). The mechanism of action of CASPR2 as a tumor suppressor gene may be similar to that of DAL-1.…”

Section: Discussionmentioning

confidence: 99%

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

et al. 2010

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Genomic translocations have been implicated in cancer.In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactinassociated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.

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Section: Discussionmentioning

confidence: 99%

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

et al. 2010

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“…Although the mechanisms by which 4.1B promotes apoptosis remain unclear, one study recently showed that overexpression of 4.1B increases caspase-8 activity in MCF-7 cells (14). Others have reported that overexpression of 4.1B induces Rac1-dependent JNK signaling (13). Recent work from our laboratory has also shown that 4.1B can interact with a potential tumor suppressor, integrin ␤8 (26), and this interaction has been confirmed in our PC-3 cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that 4.1B, or a truncated form of this protein (known as Deleted in Adenocarcinoma of the Lung-1), is frequently lost in brain, lung, and breast cancers, and that overexpression of 4.1B can inhibit the in vitro growth of tumor cell lines (9)(10)(11)(12)(13)(14). In some cases, growth suppression was associated with increased apoptosis.…”

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confidence: 99%

Protein 4.1B suppresses prostate cancer progression and metastasis

Wong

Haack

Kissil

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Protein 4.1B is a 4.1/ezrin/radixin/moesin domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers, and breast carcinomas. However, its potential tumor-suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Downregulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. Because expression of Protein 4.1B is frequently downregulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease.

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“…23 Downstream effects of protein 4.1B include activation of a JNK (c-Jun-NH2-kinase) protein, which results in reduced cell growth via decreased cyclin A expression and phosphorylation of the retinoblastoma protein. 16 Protein 4.1B has been shown to interact with the cell growth regulator protein 14-3-3. Although aggressive meningiomas show reduced levels of 14-3-3 expression, impaired 14-3-3 function has not been shown to affect protein 4.1B function, suggesting that alternative signaling pathways are present.…”

Section: Targeted Molecule Chemotherapeutic Agentsmentioning

confidence: 99%

Recent developments in chemotherapy for meningiomas: a review

Moazzam

Wagle

Zada

2013

FOC

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Object Currently, few medical options exist for refractory and atypical/anaplastic meningiomas. New developments in chemotherapeutic options for meningiomas have been explored over the past decade. The authors review these recent developments, with an emphasis on emerging avenues for therapy, clinical efficacy, and adverse effects. Methods A review of the literature was performed to identify any studies exploring recent medical and chemotherapeutic agents that have been or are currently being tested for meningiomas. Results from included preclinical and human clinical trials were reviewed and summarized. Results Current guidelines recommend only 3 drugs that can be used to treat patients with refractory and highgrade meningiomas: hydroxyurea, interferon-α 2B, and Sandostatin long-acting release. Recent developments in the medical treatment of meningiomas have been made across a variety of pharmacological classes, including cytotoxic agents, hormonal agents, immunomodulators, and targeted agents toward a variety of growth factors and their signaling cascades. Promising avenues of therapy that are being evaluated for efficacy and safety include antagonists of platelet-derived growth factor receptor, epidermal growth factor receptor, vascular endothelial growth factor receptor, and mammalian target of rapamycin. Because malignant transformation in meningiomas is likely to be mediated by numerous processes interacting via a complex matrix of signals, combination therapies affecting multiple molecular targets are currently being explored and hold significant promise as adjuvant therapy options. Conclusions Improved understanding of the molecular mechanisms driving meningioma tumorigenesis and malignant transformation has resulted in the targeted development of more specific agents for chemotherapeutic intervention in patients with nonresectable, aggressive, and malignant meningiomas.

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Protein 4.1B/Differentially Expressed in Adenocarcinoma of the Lung-1 Functions as a Growth Suppressor in Meningioma Cells by Activating Rac1-Dependent c-Jun-NH2-kinase Signaling

Cited by 35 publications

References 51 publications

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

Protein 4.1B suppresses prostate cancer progression and metastasis

Recent developments in chemotherapy for meningiomas: a review

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