AKT plays a central role in tumorigenesis

Testa, Joseph R.; Bellacosa, Alfonso

doi:10.1073/pnas.211430998

Cited by 854 publications

(682 citation statements)

References 50 publications

(37 reference statements)

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“…The PI3K/Akt/ PTEN pathway was also shown to play a role in abrogating apoptosis. Akt/ PKB is activated in a wide variety of cancers and this activation leads to the phosphorylation of a number of key apoptotic proteins thereby inactivating them (Testa and Bellacosa, 2001). …”

Section: Mitochondrial Apoptosis and Its Subversion In Oncogenesismentioning

confidence: 99%

Mitochondria and cancer: is there a morphological connection?

2006

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Mitochondria are key players in several cellular functions including growth, division, energy metabolism, and apoptosis. The mitochondrial network undergoes constant remodelling and these morphological changes are of direct relevance for the role of this organelle in cell physiology. Mitochondrial dysfunction contributes to a number of human disorders and may aid cancer progression. Here, we summarize the recent contributions made in the field of mitochondrial dynamics and discuss their impact on our understanding of cell function and tumorigenesis.

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Section: Mitochondrial Apoptosis and Its Subversion In Oncogenesismentioning

confidence: 99%

Mitochondria and cancer: is there a morphological connection?

2006

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“…There are three isoforms of the AKT (AKT1, AKT2 and AKT3), and each AKT member contains an N-terminal pleckstrin homology (PH) domain, a short a-helical linker and a C-terminal kinase domain (Testa and Bellacosa, 2001). AKTs are major downstream targets of growth factor receptors that signal through phosphatidylinositol 3-kinase (Testa and Bellacosa, 2001). Mounting evidence exists that activation of AKT proteins is important in cancer development (Muise-Helmericks et al, 1998;Dimmeler et al, 1999;Khwaja, 1999;Ozes et al, 1999;Mende et al, 2001;Wei et al, 2001).…”

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confidence: 99%

“…Mounting evidence exists that activation of AKT proteins is important in cancer development (Muise-Helmericks et al, 1998;Dimmeler et al, 1999;Khwaja, 1999;Ozes et al, 1999;Mende et al, 2001;Wei et al, 2001). PTEN inhibits AKT activation and works as a tumour suppressor (Testa and Bellacosa, 2001). Inactivating mutation of PTEN and activating mutation of PIK3CA have been detected in many human cancers and have been known as major activating mechanisms of AKTsignalling pathway in cancers (Testa and Bellacosa, 2001;Samuels et al, 2004).…”

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confidence: 99%

“…AKT1 (also known as protein kinase B) is a subfamily of serine/threonine protein kinases, and the AKT genes are the mammalian equivalent of murine viral oncogene v-akt (Testa and Bellacosa, 2001). There are three isoforms of the AKT (AKT1, AKT2 and AKT3), and each AKT member contains an N-terminal pleckstrin homology (PH) domain, a short a-helical linker and a C-terminal kinase domain (Testa and Bellacosa, 2001). AKTs are major downstream targets of growth factor receptors that signal through phosphatidylinositol 3-kinase (Testa and Bellacosa, 2001).…”

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Mutational analysis of oncogenic AKT E17K mutation in common solid cancers and acute leukaemias

et al. 2008

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Mounting evidence indicates that alterations of AKT signalling play important roles in cancer development. An earlier study discovered an oncogenic AKT1 gene mutation (AKT1 E17K) in breast, colorectal and ovarian cancers. The aim of this study was to see whether the AKT1 E17K mutation is common in breast, colorectal, lung, gastric and hepatocellular carcinomas and acute leukaemias. We analysed the presence of the AKT1 E17K mutation in 731 cancer tissues by a single-strand conformation polymorphism assay. In addition, we analysed the corresponding sequences of AKT1 E17K in AKT2 and AKT3 genes. Overall, we detected the four AKT1 E17K mutations in the breast cancers (4/93; 4.3%), but none in other cancers. There was no AKT2 or AKT3 mutation in the cancers. This study demonstrated that the AKT1 E17K mutation occurs in breast cancers at a low frequency, and that it is rare in other common cancers, including colorectal, lung, gastric and hepatocellular carcinomas and acute leukaemias. Despite the confirmed oncogenic function of the AKT1 E17K, the rare incidences of the mutation suggest that it may not play a crucial role in the development of the most common types of human cancers. (Gschwind et al, 2004). AKT1 (also known as protein kinase B) is a subfamily of serine/threonine protein kinases, and the AKT genes are the mammalian equivalent of murine viral oncogene v-akt (Testa and Bellacosa, 2001). There are three isoforms of the AKT (AKT1, AKT2 and AKT3), and each AKT member contains an N-terminal pleckstrin homology (PH) domain, a short a-helical linker and a C-terminal kinase domain (Testa and Bellacosa, 2001). AKTs are major downstream targets of growth factor receptors that signal through phosphatidylinositol 3-kinase (Testa and Bellacosa, 2001). Mounting evidence exists that activation of AKT proteins is important in cancer development (Muise-Helmericks et al, 1998;Dimmeler et al, 1999;Khwaja, 1999;Ozes et al, 1999;Mende et al, 2001;Wei et al, 2001). PTEN inhibits AKT activation and works as a tumour suppressor (Testa and Bellacosa, 2001). Inactivating mutation of PTEN and activating mutation of PIK3CA have been detected in many human cancers and have been known as major activating mechanisms of AKTsignalling pathway in cancers (Testa and Bellacosa, 2001;Samuels et al, 2004). By contrast, activating mutation of AKT genes has not been widely reported in human cancers.Recently, a research group discovered a recurrent somatic mutation of AKT1 gene in human breast, colorectal and ovarian cancers (Carpten et al, 2007). The AKT1 mutation was a missense mutation that substituted an amino acid (E17K) in the PH domain of AKT1. The AKT1 E17K mutation was found in 5 out of 61 (8.2%) breast cancers, 3 out of 51 (5.9%) colorectal cancers and 1 out of 50 (2.0%) ovarian cancers (Carpten et al, 2007). The E17K mutation was mutually exclusive with respect to PIK3CA mutation and loss of PTEN expression (Carpten et al, 2007). Functionally, the AKT1 E17K mutation stimulates AKT signalling, induces cellular transformation and produ...

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“…These are transcribed from distinct genetic loci, termed Akt1/PKBα, Akt2/PKBβ and Akt3/PKBγ. Akt family members share a similar domain structure [26] and all three proteins are expressed in all cells and tissues.…”

mentioning

confidence: 99%

Opposing roles of the oncogene Akt isoforms in tumour progression: is there a dark side to Akt pathway inhibition?

Veeriah

2012

J Chem Biol

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AKT plays a central role in tumorigenesis

Cited by 854 publications

References 50 publications

Mitochondria and cancer: is there a morphological connection?

Mitochondria and cancer: is there a morphological connection?

Mutational analysis of oncogenic AKT E17K mutation in common solid cancers and acute leukaemias

Opposing roles of the oncogene Akt isoforms in tumour progression: is there a dark side to Akt pathway inhibition?

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