The Hidden Conundrum of Phosphoinositide Signaling in Cancer

Narendra Thapa; Xiaojun Tan; Suyong Choi; Paul F. Lambert; Alan C. Rapraeger; Richard A. Anderson

doi:10.1016/j.trecan.2016.05.009

The Hidden Conundrum of Phosphoinositide Signaling in Cancer

Narendra Thapa, Xiaojun Tan, Suyong Choi, Paul F. Lambert, Alan C. Rapraeger, Richard A. Anderson

Research output: Contribution to journal › Review article › peer-review

34 Scopus citations

Abstract

Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P₃ from PI(4,5)P₂ and the subsequent activation of Akt and its downstream signaling cascades (e.g., mTORC1) dominate the landscape of the phosphoinositide signaling axis in cancer research. However, PI(4,5)P₂ is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC) and is now an established lipid messenger pivotal for various cellular events in cancer. Here we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P₂ and its generating enzymes, the phosphatidylinositol (PI) phosphate (PIP) kinases (PIPKs). We highlight how PI(4,5)P₂ and PIPKs serve as a proximal node in the phosphoinositide signaling axis and how interaction with cytoskeletal proteins regulates the migratory and invasive nexus of metastasizing tumor cells.

Original language	English (US)
Pages (from-to)	378-390
Number of pages	13
Journal	Trends in Cancer
Volume	2
Issue number	7
DOIs	https://doi.org/10.1016/j.trecan.2016.05.009
State	Published - Jul 1 2016
Externally published	Yes

Keywords

Akt
PI(3,4,5)P
PI(4,5)P
PI3K.
PIPKIγ

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.trecan.2016.05.009

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title = "The Hidden Conundrum of Phosphoinositide Signaling in Cancer",

abstract = "Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g., mTORC1) dominate the landscape of the phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC) and is now an established lipid messenger pivotal for various cellular events in cancer. Here we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol (PI) phosphate (PIP) kinases (PIPKs). We highlight how PI(4,5)P2 and PIPKs serve as a proximal node in the phosphoinositide signaling axis and how interaction with cytoskeletal proteins regulates the migratory and invasive nexus of metastasizing tumor cells.",

keywords = "Akt, PI(3,4,5)P, PI(4,5)P, PI3K., PIPKIγ",

author = "Narendra Thapa and Xiaojun Tan and Suyong Choi and Lambert, {Paul F.} and Rapraeger, {Alan C.} and Anderson, {Richard A.}",

note = "Funding Information: The authors regret not being able to include and cite the work of many investigators in the field due to space constraints. The laboratory of R.A.A. is supported by National Institutes of Health grants (CA104708 and GM057549). Support also comes from the American Heart Association (AHA) to N.T. (10POST4290052) and S.C. (13PRE14690057) and the Howard Hughes Medical Institute (HHMI) International Student Research Fellowship to X.T. The authors acknowledge the constructive comments and suggestions from colleagues in R.A.A.{\textquoteright}s laboratory, Thomas Wise and Anas Rattani. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

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doi = "10.1016/j.trecan.2016.05.009",

language = "English (US)",

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T1 - The Hidden Conundrum of Phosphoinositide Signaling in Cancer

AU - Thapa, Narendra

AU - Tan, Xiaojun

AU - Choi, Suyong

AU - Lambert, Paul F.

AU - Rapraeger, Alan C.

AU - Anderson, Richard A.

N1 - Funding Information: The authors regret not being able to include and cite the work of many investigators in the field due to space constraints. The laboratory of R.A.A. is supported by National Institutes of Health grants (CA104708 and GM057549). Support also comes from the American Heart Association (AHA) to N.T. (10POST4290052) and S.C. (13PRE14690057) and the Howard Hughes Medical Institute (HHMI) International Student Research Fellowship to X.T. The authors acknowledge the constructive comments and suggestions from colleagues in R.A.A.’s laboratory, Thomas Wise and Anas Rattani. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g., mTORC1) dominate the landscape of the phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC) and is now an established lipid messenger pivotal for various cellular events in cancer. Here we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol (PI) phosphate (PIP) kinases (PIPKs). We highlight how PI(4,5)P2 and PIPKs serve as a proximal node in the phosphoinositide signaling axis and how interaction with cytoskeletal proteins regulates the migratory and invasive nexus of metastasizing tumor cells.

AB - Phosphoinositide 3-kinase (PI3K) generation of PI(3,4,5)P3 from PI(4,5)P2 and the subsequent activation of Akt and its downstream signaling cascades (e.g., mTORC1) dominate the landscape of the phosphoinositide signaling axis in cancer research. However, PI(4,5)P2 is breaking its boundary as merely a substrate for PI3K and phospholipase C (PLC) and is now an established lipid messenger pivotal for various cellular events in cancer. Here we review the phosphoinositide signaling axis in cancer, giving due weight to PI(4,5)P2 and its generating enzymes, the phosphatidylinositol (PI) phosphate (PIP) kinases (PIPKs). We highlight how PI(4,5)P2 and PIPKs serve as a proximal node in the phosphoinositide signaling axis and how interaction with cytoskeletal proteins regulates the migratory and invasive nexus of metastasizing tumor cells.

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KW - PI3K.

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The Hidden Conundrum of Phosphoinositide Signaling in Cancer

Abstract

Keywords

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