Class I Phosphoinositide 3-Kinases in the Tumor MicroenvironmentReportar como inadecuado


Class I Phosphoinositide 3-Kinases in the Tumor Microenvironment


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The Babraham Institute, Cambridge CB22 3AT, UK





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Academic Editor: Marco Falasca

Abstract Phosphoinositide 3-kinases PI3Ks are a diverse family of enzymes which regulate various critical biological processes, such as cell proliferation and survival. Class I PI3Ks PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ mediate the phosphorylation of the inositol ring at position D3 leading to the generation of PtdIns3,4,5P3. PtdIns3,4,5P3 can be dephosphorylated by several phosphatases, of which the best known is the 3-phosphatase PTEN phosphatase and tensin homolog. The Class I PI3K pathway is frequently disrupted in human cancers where mutations are associated with increased PI3K-activity or loss of PTEN functionality within the tumor cells. However, the role of PI3Ks in the tumor stroma is less well understood. Recent evidence suggests that the white blood cell-selective PI3Kγ and PI3Kδ isoforms have an important role in regulating the immune-suppressive, tumor-associated myeloid cell and regulatory T cell subsets, respectively, and as a consequence are also critical for solid tumor growth. Moreover, PI3Kα is implicated in the direct regulation of tumor angiogenesis, and dysregulation of the PI3K pathway in stromal fibroblasts can also contribute to cancer progression. Therefore, pharmacological inhibition of the Class I PI3K family in the tumor microenvironment can be a highly attractive anti-cancer strategy and isoform-selective PI3K inhibitors may act as potent cancer immunotherapeutic and anti-angiogenic agents. View Full-Text

Keywords: PI3K; tumor microenvironment; solid cancer; cell signaling; PTEN PI3K; tumor microenvironment; solid cancer; cell signaling; PTEN





Autor: David Gyori, Tamara Chessa, Phillip T. Hawkins * and Len R. Stephens

Fuente: http://mdpi.com/



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