Aberrant mRNA translation in cancer pathogenesis: an old concept revisited comes finally of age

Pandolfi, Pier Paolo

doi:10.1038/sj.onc.1207618

Cited by 68 publications

(51 citation statements)

References 23 publications

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“…20 One possibility to explain the link between the DDX39's activity and tumorigenesis is that simulation of RNA export/splicing by DDX39 aids in neoplastic transformation through the increase in the translational level because aberrant or enhanced translation is recently recognized as a molecular basis of transformation. 23 As expected, overexpression of DDX39-L augmented expression of the intron-encoded CAT gene (Fig. 6A) that is frequently used for the assessment of RNA export factors.…”

Section: Discussionsupporting

confidence: 73%

“…The stimulation of RNA splicing/export should increase the amount of cytosolic mRNA and concomitantly the translational efficiency. In light of the connection of elevated translation with tumor transformation, 23 we reasoned that the acceleration of cancer cell growth by DDX39-L is mediated through an elevated translational rate. To address the issue, we investigated the effects of DDX39-L on expression of reporter genes.…”

Section: © 2 0 0 7 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

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DDX39, upregulated in lung squamous cell cancer, displays RNA helicase activities and promotes cancer cell growth

Sugiura

Nagano²,

Noguchi³

2007

Cancer Biology & Therapy

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KeY wordSDDX39, DEAD box proteins, lung squamous cell carcinoma, microarray; RNA helicase AbbreviATioNS HNBEhuman normal bronchial epithelial cells LAC lung adenocarcinoma LSCC lung squamous cell carcinoma MGFP monster green fluorescent protein NSCLC non-small-cell lung cancer AcKNowledgemeNTSWe thank Drs. Shigeaki Katoh and Thomas J. Hope for their kind gifts (pCH110 and pDM138, respectively) and Dr. Kentaro Miyamoto for image visualization. We are also indebted to Aya Yamaguchi and Rie Ikeda for sequencing. [Cancer Biology & Therapy 6:6, 957-964; June 2007]; ©2007 Landes Bioscience AbSTrcTTo explore differentially expressed genes involved in non-small cell lung cancer progression, we used the gene expression profile database of various human tissues and identified DDX39, a new member of the DEAD box RNA helicases, showing overexpression in human lung squamous cell carcinoma (LSCC) but not in lung adenocarcinoma (LAC). There existed three types of alternatively spliced DDX39 variants (DDX39-L, -S and -SS), of which only DDX39-L contains all the motifs required for RNA helicase activity. RT-PCR analysis verified the increased expression of DDX39-L in LSCC, but not LAC, cultured cells compared with normal bronchial epithelial cells. A high sequence similarity to UAP56 and punctate nuclear localization pattern of DDX39-L suggest that it plays a role in RNA splicing/export. Recombinant DDX39-L binds RNA, hydrolyzes NTPs in an RNA-dependent manner and unwinds double strand RNA bidirectionally, proving that DDX39 is an RNA helicase. Overexpression of DDX39-L stimulates colony formation of HeLa cells, probably through elevation of a translational level, indicating the biological significance of DDX39 in cancer pathogenesis. Thus, DDX39 is a novel RNA helicase capable of promoting cancer cell growth and, thereby, can be a potential target for development of a therapeutic strategy for LSCC.

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Section: Discussionsupporting

confidence: 73%

Section: © 2 0 0 7 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

DDX39, upregulated in lung squamous cell cancer, displays RNA helicase activities and promotes cancer cell growth

Sugiura

Nagano²,

Noguchi³

2007

Cancer Biology & Therapy

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show abstract

“…PI3K signaling stimulates phosphorylation of the 4E-BP's which then disassociate from eIF4E (the cap-binding protein of eIF4F), and release it, resulting in the stimulation of translation initiation. Loss of function of PTEN, an inhibitor of PI3K function, has been reported to occur in a number of tumors and correlates with the hyperphosphorylation of eIF4E (Bjornsti and Houghton, 2004;Pandolfi, 2004). One way 4E-BP phsophorylation can occur is through interaction with a PI3-like kinase TOR (target of rapamycin, also referred to as FKBP12-rapamycin-associated protein).…”

Section: Translation and Cancermentioning

confidence: 99%

VSV-tumor selective replication and protein translation

2005

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“…In the past five years, it has become evident that cancer is also subject to translational control. [3][4][5][6][7][8][9][10][11] As a result, attention has focused on the rate-limiting step in the process of protein synthesis, translation initiation. Here, we will discuss cancer-related regulatory events mediated by the mRNA binding stage of translation initiation.…”

Section: Introductionmentioning

confidence: 99%

The Cap-Dependent Translation Apparatus Integrates and Amplifies Cancer Pathways

Polunovsky¹,

Bitterman²

2006

RNA Biology

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Aberrant mRNA translation in cancer pathogenesis: an old concept revisited comes finally of age

Cited by 68 publications

References 23 publications

DDX39, upregulated in lung squamous cell cancer, displays RNA helicase activities and promotes cancer cell growth

DDX39, upregulated in lung squamous cell cancer, displays RNA helicase activities and promotes cancer cell growth

VSV-tumor selective replication and protein translation

The Cap-Dependent Translation Apparatus Integrates and Amplifies Cancer Pathways

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