Phosphoinositide 3-kinase in disease: timing, location, and scaffolding

Wymann, Matthias P.; Marone, Romina

doi:10.1016/j.ceb.2005.02.011

Cited by 191 publications

(154 citation statements)

References 59 publications

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“…Many known oncogenes, such as mutated ERBB, insulin-like growth factor-1 (IGF1), c-Kit (stem-cell factor receptor), overexpressed chemokine receptors, mutated Ras, BCR-ABL and elevated levels of the proto-oncogene Src, to name but a few, provide constitutive input signals to PI3K 6,30 . The finding that the 3-lipid phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome ten) is frequently mutated in numerous late-stage tumours finally demonstrated that elevated levels of PtdIns(3,4,5)P 3 contribute to oncogenesis 31,32 .…”

Section: Dysregulated Lipid Signalling In Cancermentioning

confidence: 99%

Lipid signalling in disease

Wymann

Schneiter

2008

Nat Rev Mol Cell Biol

1,106

906

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Section: Dysregulated Lipid Signalling In Cancermentioning

confidence: 99%

Lipid signalling in disease

Wymann

Schneiter

2008

Nat Rev Mol Cell Biol

1,106

906

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“…The PI3K-PKB signalling cascade is a key pathway by which cells may respond to a wide range of stimuli, which may be generated intrinsically (for example, growth factors, cytokines and cell-cell contact) or from an external source (for example, irradiation, and physical or genotoxic stress) (Leevers et al, 1999;Hennessy et al, 2005;Wymann and Marone, 2005;Samuels and Ericson, 2006). At the molecular level, many of the PI3K-PKB-mediated mitogenic responses are achieved through the direct repression of FoxO transcription factors by PKB-mediated phosphorylation, promoting nuclear export, proteosomal degradation and a decrease in transactivation activity (Brunet et al, 1999(Brunet et al, , 2001Kops et al, 2002b;Jacobs et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Many forks in the path: cycling with FoxO

2008

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FoxO transcription factors are an evolutionary conserved subfamily of the forkhead transcription factors, characterized by the forkhead DNA-binding domain. FoxO factors regulate a number of cellular processes involved in cell-fate decisions in a cell-type-and environment-specific manner, including metabolism, differentiation, apoptosis and proliferation. A key mechanism by which FoxO determines cell fate is through regulation of the cell cycle machinery, and as such the cellular consequence of FoxO deregulation is often manifested through perturbation of the cell cycle. Consequently, the deregulation of FoxO factors is implicated in the development of numerous proliferative diseases, in particular cancer.

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“…The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is activated in multiple cancers, leading to oncogenic transformation (Vivanco and Sawyers, 2002;Bader et al, 2005;Wymann and Marone, 2005). Activation may result from activating mutations in PI3-kinase genes or inactivating mutations in the tumor suppressor gene PTEN (phosphatase and tensin homolog).…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Abubaker¹,

Bavi²,

Al-harbi³

et al. 2008

Oncogene

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Activation of the phosphatidylinositol 3 0 -kinase (PI3K)/ AKT pathway results in an increase in cell proliferation and survival. Somatic mutations within the PI3K catalytic subunit, PIK3CA are common cause of increasing PI3K activity and are believed to be oncogenic in many cancer types. Few reports addressed the association between PIK3CA mutations and tumor progression specifically in microsatellite instable (MSI) colorectal cancer (CRC). In the present study, we have evaluated PIK3CA mutational status in a series of 410 Middle Eastern CRC and 13 colon cell lines to study the prevalence of PIK3CA mutations in MSI cases, PTEN expression in CRC and possibility of therapeutic targeting of this set of patients. PIK3CA mutations were found in four of the cell lines tested and 51 colorectal carcinomas (12.2%). Three of these four mutated cell lines were MSI. PTEN was inactivated in 66.1% of the CRC. Furthermore, we observed a strong association between PIK3CA mutations and MSI status (P ¼ 0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P ¼ 0.043). A high prevalence of genetic alterations in PI3K/AKT pathway in Saudi cohort of CRC, predominance of PIK3CA mutations in the MSI subgroup and their possible involvement in development/progression of this subset of CRC are some of the significant findings of our study.

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Phosphoinositide 3-kinase in disease: timing, location, and scaffolding

Cited by 191 publications

References 59 publications

Lipid signalling in disease

Lipid signalling in disease

Many forks in the path: cycling with FoxO

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

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