<i>Glioma Pathogenesis-Related Protein 1</i> Exerts Tumor Suppressor Activities through Proapoptotic Reactive Oxygen Species–c-Jun–NH2 Kinase Signaling

Li, Likun; Fattah, Elmoataz Abdel; Cao, Guangwen; Ren, Chengzhen; Yang, Guang; Goltsov, Alexei A.; Chinault, A. Craig; Cai, Wei-Wen; Timme, Terry L.; Thompson, Timothy C.

doi:10.1158/0008-5472.can-07-2931

Cited by 60 publications

(84 citation statements)

References 50 publications

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“…11 A deficiency in TAP has been linked to several cancers, including breast and prostate cancer. 11,23,27 We previously found that the expression of TAP is significantly downregulated in prostate cancer, which is associated with tumor cell proliferation, as well as with an increased risk of cancer recurrence. 23,24 Overexpression of TAP inhibits prostate cancer growth in the absence of vitamin E both in vitro and in vivo through suppression of the PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

Cross‐talk of alpha tocopherol‐associated protein and JNK controls the oxidative stress‐induced apoptosis in prostate cancer cells

Zhu

et al. 2012

Intl Journal of Cancer

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Excess intracellular reactive oxygen species (ROS) beyond a threshold can induce apoptosis in cancer cells. However, the signal pathways that can augment the proapoptotic function of ROS remain largely unknown. We previously identified a tumor suppressor, alpha-tocopherol-associated protein (TAP), yet little is known regarding the role of TAP in the apoptotic signaling in prostate cancer. Interestingly, we recently found that exposure of prostate cancer cells to hydrogen peroxide (H 2 O 2 ) resulted in induced apoptosis as well as increased expression of TAP. Small interfering RNA (siRNA) mediated silencing of endogenous TAP expression conferred effective protection from H 2 O 2 -induced apoptosis. Further mechanistic study showed exposure of prostate cancer cells to H 2 O 2 resulted in increased phosphorylation of both JNK and c-Jun, and TAP siRNA effectively decreased H 2 O 2 -induced JNK and c-Jun phosphorylation. Immunoprecipitation experiments revealed that JNK physically associates with TAP. Furthermore, signaling downstream of JNK to the AP-1 complex and BH-3-only subfamily were found to be regulated on changing the TAP expression status. TAP could also promote the oxidative stress-induced apoptosis effect of docetaxel. In the mice xenograft model, H 2 O 2 treatment induced TAP expression, JNK phosphorylation and apoptosis of prostate cancer. Recombinant adeno-associated virus 2 (rAAV2)-TAP injection significantly sensitizes this H 2 O 2 proapoptotic effect. Together, we have identified a novel functional mechanism that the cross-talk of TAP-JNK is involved in oxidative stress-induced apoptosis in prostate cancer cells. Disrupting the redox balance of cancer cells by this signaling may enable therapeutic selectivity and provide benefit to overcome the drug resistance of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Cross‐talk of alpha tocopherol‐associated protein and JNK controls the oxidative stress‐induced apoptosis in prostate cancer cells

Zhu

et al. 2012

Intl Journal of Cancer

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“…MEKK2 is involved in JNK and ERK5 activation, and JNK activation can promote apoptosis in GBM cells (12,19).…”

Section: Mir-26a Inhibits Map3k2/mekk2 Expression and Jnk-dependentmentioning

confidence: 99%

“…We also identified MAP3K2/MEKK2, an activator of the JNK pathway, which has been implicated in apoptosis and tumor suppression (13,19). Thus, PTEN, RB1, and MAP3K2/MEKK2 were chosen for further study.…”

mentioning

confidence: 99%

Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship

Kim

Huang

Jiang

et al. 2010

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

223

173

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Using a multidimensional genomic data set on glioblastoma from The Cancer Genome Atlas, we identified hsa-miR-26a as a cooperating component of a frequently occurring amplicon that also contains CDK4 and CENTG1, two oncogenes that regulate the RB1 and PI3 kinase/AKT pathways, respectively. By integrating DNA copy number, mRNA, microRNA, and DNA methylation data, we identified functionally relevant targets of miR-26a in glioblastoma, including PTEN, RB1, and MAP3K2/MEKK2. We demonstrate that miR-26a alone can transform cells and it promotes glioblastoma cell growth in vitro and in the mouse brain by decreasing PTEN, RB1, and MAP3K2/MEKK2 protein expression, thereby increasing AKT activation, promoting proliferation, and decreasing c-JUN Nterminal kinase-dependent apoptosis. Overexpression of miR-26a in PTEN-competent and PTEN-deficient glioblastoma cells promoted tumor growth in vivo, and it further increased growth in cells overexpressing CDK4 or CENTG1. Importantly, glioblastoma patients harboring this amplification displayed markedly decreased survival. Thus, hsa-miR-26a, CDK4, and CENTG1 comprise a functionally integrated oncomir/oncogene DNA cluster that promotes aggressiveness in human cancers by cooperatively targeting the RB1, PI3K/AKT, and JNK pathways.

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“…Overexpression of GLIPR1 in cancer cells leads to suppression of colony growth and induction of apoptosis. Mechanistic analysis indicates that GLIPR1 up-regulation increases the production of ROS, leading to apoptosis through activation of the JNK signaling cascade [56] . However, in p38-related apoptosis that is independent of ROS generation, JNK seems to execute a reverse function.…”

Section: Ros Involve Apoptosis That Relates To the P38 Pathwaymentioning

confidence: 99%

Reactive oxygen species: A double-edged sword in oncogenesis

Pan¹,

Hong²,

Ren³

2009

WJG

206

133

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Reactive oxygen species (ROS) are molecules or ions formed by the incomplete one-electron reduction of oxygen. Of interest, it seems that ROS manifest dual roles, cancer promoting or cancer suppressing, in tumorigenesis. ROS participate simultaneously in two signaling pathways that have inverse functions in tumorigenesis, Ras-Raf-MEK1/2-ERK1/2 signaling and the p38 mitogen-activated protein kinases (MAPK) pathway. It is well known that Ras-Raf-MEK1/2-ERK1/2 signaling is related to oncogenesis, while the p38 MAPK pathway contributes to cancer suppression, which involves oncogene-induced senescence, inflammationinduced cellular senescence, replicative senescence, contact inhibition and DNA-damage responses. Thus, ROS may not be an absolute carcinogenic factor or cancer suppressor. The purpose of the present review is to discuss the dual roles of ROS in the pathogenesis of cancer, and the signaling pathway mediating their role in tumorigenesis.

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Glioma Pathogenesis-Related Protein 1 Exerts Tumor Suppressor Activities through Proapoptotic Reactive Oxygen Species–c-Jun–NH2 Kinase Signaling

Cited by 60 publications

References 50 publications

Cross‐talk of alpha tocopherol‐associated protein and JNK controls the oxidative stress‐induced apoptosis in prostate cancer cells

Cross‐talk of alpha tocopherol‐associated protein and JNK controls the oxidative stress‐induced apoptosis in prostate cancer cells

Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship

Reactive oxygen species: A double-edged sword in oncogenesis

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