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Intestinal Tumorigenesis pp 101–135Cite as

The Role of PI3K Signaling Pathway in Intestinal Tumorigenesis

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Abstract

The phosphoinositide 3-kinases (PI3K) are a family of signaling enzymes that regulate multiple key cellular functions including cell cycle progression, growth, migration, apoptosis, and vesicular trafficking. Components of this pathway are necessary for normal growth and development, but due to both genetic and metabolic changes, this pathway can become dysregulated as early as the fetal period. Continued alterations of the PI3K pathway can frequently lead to activation of cancer development and metastasis. As more information is discovered about the components of this pathway and their signaling mechanisms we have opportunities to exploit multiple sites of the cascade, and develop targeted inhibitors against these small molecules. A thorough understanding of this pathway and its signaling mechanisms is paramount to the development of new and improved treatments for intestinal cancers.

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Abbreviations

4E-BP:

Eukaryotic translation initiation factor 4E-binding protein

5-FU:

5-fluorouracil

BMP:

Bone morphogenetic protein

CCK2R:

Gastrin/cholecystokinin-2 receptor

c-FLIP:

A master anti-apoptotic regulator

DNA-PK:

DNA-dependent protein kinase

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptors

EMT:

Epithelial-mesenchymal transition

FasL:

A type-II transmembrane protein of tumor necrosis factor

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

FOXO:

Forkhead box subgroup O

GI:

Gastrointestinal

GISTs:

Gastrointestinal stromal tumors

GPCR:

G-protein couple receptors

GSK3β:

Glycogen synthase kinase-3 beta

GTP:

Guanosine triphosphate

HER2:

Human epidermal growth factor receptor 2

IGF-1:

Insulin like growth factor 1

LY294002:

2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one

mTOR:

Mammalian target of rapamycin

mTORC:

mTOR complex (mTORC1 and mTORC2)

PDK1:

3-phosphoinositide dependent protein kinase-1

PH:

Pleckstrin homology

PHLPP:

PH domain and leucine rich repeat protein phosphatases

PI3K:

Phosphatidylinositide 3-kinase

PIK3CA:

Gene encoding p110α

PIK3R1:

Gene encoding p85α

PIP2 :

Phosphatidylinositol 4,5-bisphosphate

PIP3 :

Phosphatidylinositol (3, 4, 5) phosphate

PP2A:

Protein phosphatase 2A

PTEN:

Phosphatase and tensin homolog

Rheb:

Ras homolog enriched in brain

RICTOR:

Rapamycin insensitive component of mTOR

RTK:

Receptor tyrosine kinase

S6K:

S6 kinase

SCCE:

Squamous cell carcinoma of the esophagus

SH2:

Src-homology 2

TM:

Transmembrane

TSC:

Tuberous sclerosis complex

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

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Authors and Affiliations

  1. Department of Surgery, University of Kentucky, Lexington, KY, USA

    Jennifer W. Harris MD

  2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA

    Tianyan Gao PhD

  3. Department of Surgery, Markey Cancer Center, University of Kentucky, Lexington, KY, USA

    B. Mark Evers MD

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  1. Jennifer W. Harris MD
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  2. Tianyan Gao PhD
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  3. B. Mark Evers MD
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Correspondence to Jennifer W. Harris MD .

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Editors and Affiliations

  1. Department of Medicine, Stony Brook University, Stony Brook, USA

    Vincent W. Yang

  2. Department of Medicine, Stony Brook University, Stony Brook, New York, USA

    Agnieszka B. Bialkowska

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Harris, J., Gao, T., Evers, B. (2015). The Role of PI3K Signaling Pathway in Intestinal Tumorigenesis. In: Yang, V., Bialkowska, A. (eds) Intestinal Tumorigenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-19986-3_4

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