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Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer

The phosphoinositide 3-kinase (PI3K) signalling pathway is highly dysregulated in cancer, leading to elevated PI3K signalling and altered cellular processes that contribute to tumour development. The pathway is normally orchestrated by class I PI3K enzymes and negatively regulated by the phosphatase...

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Autores principales: Mazloumi Gavgani, Fatemeh, Smith Arnesen, Victoria, Jacobsen, Rhîan G., Krakstad, Camilla, Hoivik, Erling A., Lewis, Aurélia E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321576/
https://www.ncbi.nlm.nih.gov/pubmed/30544563
http://dx.doi.org/10.3390/ijms19123931
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author Mazloumi Gavgani, Fatemeh
Smith Arnesen, Victoria
Jacobsen, Rhîan G.
Krakstad, Camilla
Hoivik, Erling A.
Lewis, Aurélia E.
author_facet Mazloumi Gavgani, Fatemeh
Smith Arnesen, Victoria
Jacobsen, Rhîan G.
Krakstad, Camilla
Hoivik, Erling A.
Lewis, Aurélia E.
author_sort Mazloumi Gavgani, Fatemeh
collection PubMed
description The phosphoinositide 3-kinase (PI3K) signalling pathway is highly dysregulated in cancer, leading to elevated PI3K signalling and altered cellular processes that contribute to tumour development. The pathway is normally orchestrated by class I PI3K enzymes and negatively regulated by the phosphatase and tensin homologue, PTEN. Endometrial carcinomas harbour frequent alterations in components of the pathway, including changes in gene copy number and mutations, in particular in the oncogene PIK3CA, the gene encoding the PI3K catalytic subunit p110α, and the tumour suppressor PTEN. PIK3CB, encoding the other ubiquitously expressed class I isoform p110β, is less frequently altered but the few mutations identified to date are oncogenic. This isoform has received more research interest in recent years, particularly since PTEN-deficient tumours were found to be reliant on p110β activity to sustain transformation. In this review, we describe the current understanding of the common and distinct biochemical properties of the p110α and p110β isoforms, summarise their mutations and highlight how they are targeted in clinical trials in endometrial cancer.
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spelling pubmed-63215762019-01-07 Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer Mazloumi Gavgani, Fatemeh Smith Arnesen, Victoria Jacobsen, Rhîan G. Krakstad, Camilla Hoivik, Erling A. Lewis, Aurélia E. Int J Mol Sci Review The phosphoinositide 3-kinase (PI3K) signalling pathway is highly dysregulated in cancer, leading to elevated PI3K signalling and altered cellular processes that contribute to tumour development. The pathway is normally orchestrated by class I PI3K enzymes and negatively regulated by the phosphatase and tensin homologue, PTEN. Endometrial carcinomas harbour frequent alterations in components of the pathway, including changes in gene copy number and mutations, in particular in the oncogene PIK3CA, the gene encoding the PI3K catalytic subunit p110α, and the tumour suppressor PTEN. PIK3CB, encoding the other ubiquitously expressed class I isoform p110β, is less frequently altered but the few mutations identified to date are oncogenic. This isoform has received more research interest in recent years, particularly since PTEN-deficient tumours were found to be reliant on p110β activity to sustain transformation. In this review, we describe the current understanding of the common and distinct biochemical properties of the p110α and p110β isoforms, summarise their mutations and highlight how they are targeted in clinical trials in endometrial cancer. MDPI 2018-12-07 /pmc/articles/PMC6321576/ /pubmed/30544563 http://dx.doi.org/10.3390/ijms19123931 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mazloumi Gavgani, Fatemeh
Smith Arnesen, Victoria
Jacobsen, Rhîan G.
Krakstad, Camilla
Hoivik, Erling A.
Lewis, Aurélia E.
Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
title Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
title_full Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
title_fullStr Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
title_full_unstemmed Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
title_short Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
title_sort class i phosphoinositide 3-kinase pik3ca/p110α and pik3cb/p110β isoforms in endometrial cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321576/
https://www.ncbi.nlm.nih.gov/pubmed/30544563
http://dx.doi.org/10.3390/ijms19123931
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