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

• Published in: International journal of molecular sciences 2018-12, Vol.19 (12), p.3931
• Main Authors: Mazloumi Gavgani, Fatemeh, Smith Arnesen, Victoria, Jacobsen, Rhîan G, Krakstad, Camilla, Hoivik, Erling A, Lewis, Aurélia E
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Cancer; Carcinoma; Cell growth; Clinical trials; Copy number; Endometrial cancer; Endometrium; Homology; Isoforms; Kinases; Mutation; p110α; p110β; phosphoinositide 3-kinase; PIK3CA; PIK3CB; PTEN protein; Review; Signal transduction; Tensin; Tumor suppressor genes; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123931

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 , the gene encoding the PI3K catalytic subunit p110α, and the tumour suppressor . , 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.