Nature Reviews Cancer, volume 20, issue 2, pages 74-88
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
1
Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, USA
|
2
Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, USA
|
Publication type: Journal Article
Publication date: 2019-11-04
Journal:
Nature Reviews Cancer
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 78.5
ISSN: 1474175X, 14741768
PubMed ID:
31686003
General Environmental Science
General Earth and Planetary Sciences
Abstract
The altered metabolic programme of cancer cells facilitates their cell-autonomous proliferation and survival. In normal cells, signal transduction pathways control core cellular functions, including metabolism, to couple the signals from exogenous growth factors, cytokines or hormones to adaptive changes in cell physiology. The ubiquitous, growth factor-regulated phosphoinositide 3-kinase (PI3K)–AKT signalling network has diverse downstream effects on cellular metabolism, through either direct regulation of nutrient transporters and metabolic enzymes or the control of transcription factors that regulate the expression of key components of metabolic pathways. Aberrant activation of this signalling network is one of the most frequent events in human cancer and serves to disconnect the control of cell growth, survival and metabolism from exogenous growth stimuli. Here we discuss our current understanding of the molecular events controlling cellular metabolism downstream of PI3K and AKT and of how these events couple two major hallmarks of cancer: growth factor independence through oncogenic signalling and metabolic reprogramming to support cell survival and proliferation. This Review discusses the PI3K–AKT signalling network and its control of cancer cell metabolism through both direct and indirect regulation of nutrient transport and metabolic enzymes, thereby connecting oncogenic signalling and metabolic reprogramming to support cancer cell survival and proliferation.
Citations by journals
|
10
20
30
40
50
60
|
|
|
International Journal of Molecular Sciences
|
International Journal of Molecular Sciences
53 publications, 5.22%
|
|
Cancers
|
Cancers
48 publications, 4.73%
|
|
Frontiers in Oncology
|
Frontiers in Oncology
35 publications, 3.45%
|
|
Cells
|
Cells
21 publications, 2.07%
|
|
Frontiers in Cell and Developmental Biology
|
Frontiers in Cell and Developmental Biology
20 publications, 1.97%
|
|
Frontiers in Immunology
|
Frontiers in Immunology
16 publications, 1.58%
|
|
Frontiers in Pharmacology
|
Frontiers in Pharmacology
12 publications, 1.18%
|
|
Cell Death and Disease
|
Cell Death and Disease
12 publications, 1.18%
|
|
Biomedicine and Pharmacotherapy
|
Biomedicine and Pharmacotherapy
12 publications, 1.18%
|
|
Scientific Reports
|
Scientific Reports
10 publications, 0.99%
|
|
Nature Communications
|
Nature Communications
9 publications, 0.89%
|
|
Journal of Translational Medicine
|
Journal of Translational Medicine
8 publications, 0.79%
|
|
Aging
|
Aging
7 publications, 0.69%
|
|
Genes
|
Genes
7 publications, 0.69%
|
|
Journal of Biological Chemistry
|
Journal of Biological Chemistry
7 publications, 0.69%
|
|
Cancer Research
|
Cancer Research
7 publications, 0.69%
|
|
Antioxidants
|
Antioxidants
6 publications, 0.59%
|
|
Biomolecules
|
Biomolecules
6 publications, 0.59%
|
|
Molecular Cancer
|
Molecular Cancer
6 publications, 0.59%
|
|
Metabolites
|
Metabolites
5 publications, 0.49%
|
|
Molecules
|
Molecules
5 publications, 0.49%
|
|
Journal of Cellular Physiology
|
Journal of Cellular Physiology
5 publications, 0.49%
|
|
BMC Cancer
|
BMC Cancer
5 publications, 0.49%
|
|
Cancer and Metastasis Reviews
|
Cancer and Metastasis Reviews
5 publications, 0.49%
|
|
Cancer Cell International
|
Cancer Cell International
5 publications, 0.49%
|
|
Cellular and Molecular Life Sciences
|
Cellular and Molecular Life Sciences
5 publications, 0.49%
|
|
Heliyon
|
Heliyon
5 publications, 0.49%
|
|
Advanced Science
|
Advanced Science
5 publications, 0.49%
|
|
Life Sciences
|
Life Sciences
5 publications, 0.49%
|
|
10
20
30
40
50
60
|
Citations by publishers
|
20
40
60
80
100
120
140
160
180
200
|
|
|
Springer Nature
|
Springer Nature
191 publications, 18.82%
|
|
Elsevier
|
Elsevier
191 publications, 18.82%
|
|
Multidisciplinary Digital Publishing Institute (MDPI)
|
Multidisciplinary Digital Publishing Institute (MDPI)
179 publications, 17.64%
|
|
Frontiers Media S.A.
|
Frontiers Media S.A.
107 publications, 10.54%
|
|
Wiley
|
Wiley
73 publications, 7.19%
|
|
Hindawi Limited
|
Hindawi Limited
16 publications, 1.58%
|
|
Taylor & Francis
|
Taylor & Francis
14 publications, 1.38%
|
|
American Association for Cancer Research (AACR)
|
American Association for Cancer Research (AACR)
14 publications, 1.38%
|
|
Spandidos Publications
|
Spandidos Publications
11 publications, 1.08%
|
|
American Chemical Society (ACS)
|
American Chemical Society (ACS)
10 publications, 0.99%
|
|
American Society for Biochemistry and Molecular Biology
|
American Society for Biochemistry and Molecular Biology
9 publications, 0.89%
|
|
Impact Journals
|
Impact Journals
8 publications, 0.79%
|
|
Wolters Kluwer Health
|
Wolters Kluwer Health
7 publications, 0.69%
|
|
AME Publishing Company
|
AME Publishing Company
6 publications, 0.59%
|
|
SAGE
|
SAGE
5 publications, 0.49%
|
|
Neoplasia Press
|
Neoplasia Press, 5, 0.49%
Neoplasia Press
5 publications, 0.49%
|
|
Public Library of Science (PLoS)
|
Public Library of Science (PLoS)
5 publications, 0.49%
|
|
American Association for the Advancement of Science (AAAS)
|
American Association for the Advancement of Science (AAAS)
5 publications, 0.49%
|
|
Dove Medical Press
|
Dove Medical Press
5 publications, 0.49%
|
|
American Society of Hematology
|
American Society of Hematology
5 publications, 0.49%
|
|
Future Medicine
|
Future Medicine
3 publications, 0.3%
|
|
The Royal Society
|
The Royal Society
3 publications, 0.3%
|
|
eLife Sciences Publications
|
eLife Sciences Publications
3 publications, 0.3%
|
|
Oxford University Press
|
Oxford University Press
3 publications, 0.3%
|
|
American Physiological Society
|
American Physiological Society
3 publications, 0.3%
|
|
American Society for Clinical Investigation
|
American Society for Clinical Investigation
2 publications, 0.2%
|
|
Bentham Science
|
Bentham Science
2 publications, 0.2%
|
|
The Company of Biologists
|
The Company of Biologists
2 publications, 0.2%
|
|
Portland Press
|
Portland Press
2 publications, 0.2%
|
|
20
40
60
80
100
120
140
160
180
200
|
- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
{"yearsCitations":{"type":"bar","data":{"show":true,"labels":[2020,2021,2022,2023,2024],"ids":[0,0,0,0,0],"codes":[0,0,0,0,0],"imageUrls":["","","","",""],"datasets":[{"label":"Citations number","data":[76,254,295,305,85],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":["7.49","25.02","29.06","30.05","8.37"],"barThickness":null}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"journals":{"type":"bar","data":{"show":true,"labels":["International Journal of Molecular Sciences","Cancers","Frontiers in Oncology","Cells","Frontiers in Cell and Developmental Biology","Frontiers in Immunology","Frontiers in Pharmacology","Cell Death and Disease","Biomedicine and Pharmacotherapy","Scientific Reports","Nature Communications","Journal of Translational Medicine","Aging","Genes","Journal of Biological Chemistry","Cancer Research","Antioxidants","Biomolecules","Molecular Cancer","Metabolites","Molecules","Journal of Cellular Physiology","BMC Cancer","Cancer and Metastasis Reviews","Cancer Cell International","Cellular and Molecular Life Sciences","Heliyon","Advanced Science","Life Sciences"],"ids":[14627,22471,10990,25293,12128,1699,9788,25236,23951,13767,3231,18128,780,8879,19451,11199,16381,13780,21240,17024,1770,4815,6868,18048,9737,5151,21848,4130,2527],"codes":[0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/HY0CXgRt044tzIAB16PDvDzdHeKHGtSvlMH0yWf6_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/OuA6WPZekwEiUM99mP2pSqj4yHPxHezM6xgLhAjO_medium.webp","\/storage\/images\/resized\/cfuVw6XIq2mATDNJdXiose3W8qYbkmaVSpHoP8XL_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp"],"datasets":[{"label":"","data":[53,48,35,21,20,16,12,12,12,10,9,8,7,7,7,7,6,6,6,5,5,5,5,5,5,5,5,5,5],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[5.22,4.73,3.45,2.07,1.97,1.58,1.18,1.18,1.18,0.99,0.89,0.79,0.69,0.69,0.69,0.69,0.59,0.59,0.59,0.49,0.49,0.49,0.49,0.49,0.49,0.49,0.49,0.49,0.49],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Journals","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"publishers":{"type":"bar","data":{"show":true,"labels":["Springer Nature","Elsevier","Multidisciplinary Digital Publishing Institute (MDPI)","Frontiers Media S.A.","Wiley","Hindawi Limited","Taylor & Francis","American Association for Cancer Research (AACR)","Spandidos Publications","American Chemical Society (ACS)","American Society for Biochemistry and Molecular Biology","Impact Journals","Wolters Kluwer Health","AME Publishing Company","SAGE","Neoplasia Press","Public Library of Science (PLoS)","American Association for the Advancement of Science (AAAS)","Dove Medical Press","American Society of Hematology","Future Medicine","The Royal Society","eLife Sciences Publications","Oxford University Press","American Physiological Society","American Society for Clinical Investigation","Bentham Science","The Company of Biologists","Portland Press"],"ids":[8,17,202,208,11,6921,18,2286,1097,40,2090,342,32,1566,31,4513,344,189,417,2252,6949,259,6627,19,166,564,39,872,801],"codes":[0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/hqfzhQAjTGlNSRs6yzFNITgjSMm9Jr2QuotJHIvE_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/cfuVw6XIq2mATDNJdXiose3W8qYbkmaVSpHoP8XL_medium.webp","\/storage\/images\/resized\/8zKfOwdd5XirYzTQfqwp7U8IEQc8ckIOjyYQSBkk_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/OuA6WPZekwEiUM99mP2pSqj4yHPxHezM6xgLhAjO_medium.webp","\/storage\/images\/resized\/HY0CXgRt044tzIAB16PDvDzdHeKHGtSvlMH0yWf6_medium.webp","\/storage\/images\/resized\/6QE8LXWrLpkoy5A2te6hw7who46GeCoTYIstuoAz_medium.webp","\/storage\/images\/resized\/PYBAYQjpFdxPQPRGY3kU5Xzbu0W7K7umVNk0TY9i_medium.webp","\/storage\/images\/resized\/ruydfaB80LDjlkYqsfOeUAZohOIODyq7bQzis5O7_medium.webp","","\/storage\/images\/resized\/PRGhlgB4OKRltSNtT39eA6wlnOTGRap1QQ6FQHih_medium.webp","\/storage\/images\/resized\/s10mcsCV4OAUg9O2KrqOquQC0PhyLMI8hUUkuflM_medium.webp","\/storage\/images\/resized\/wVWp6zaxUsMdR03dYMdOZoesUrVGtNMWkHKByIvT_medium.webp","\/storage\/images\/resized\/QMhhcrIUiVtFnND3WWZ7hIbu6GYeoRoA2zoVsMEX_medium.webp","\/storage\/images\/resized\/AN2jnDN59NmKaS4CWLHAGstADL2DbnatQScsFA6C_medium.webp","\/storage\/images\/resized\/BHBStD1OkQqtKFRRjS5njgNe7bXCAEgaDQVK7GTA_medium.webp","\/storage\/images\/resized\/eIZgkq1MRZyJ3hBkdupnUUv7wgB6zCl9D99SlPN5_medium.webp","\/storage\/images\/resized\/yNSijlgQghQF53VZuyFLA30CKDe4j3HK74Vtpnxa_medium.webp","\/storage\/images\/resized\/eZQGZ1aBN8Xm8Yr5YG7nBeNQtWLPrca5SfDreLbq_medium.webp","\/storage\/images\/resized\/aFa86lAy63Pq5tYKiOsH017UsgJA6uk6ed66C0Ns_medium.webp","\/storage\/images\/resized\/doUaFUZdxUEQjLi1TwZjGHi8HXYNWWSk04dSC6Xh_medium.webp","\/storage\/images\/resized\/ko5EaisKGm66J1hHXtfEgVEeeWb9uOcMofpNuf0a_medium.webp","\/storage\/images\/resized\/nUqNrP9GnM1t0BrAIXp1LBodjU8aIJ2Fk4pLfGhZ_medium.webp"],"datasets":[{"label":"","data":[191,191,179,107,73,16,14,14,11,10,9,8,7,6,5,5,5,5,5,5,3,3,3,3,3,2,2,2,2],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[18.82,18.82,17.64,10.54,7.19,1.58,1.38,1.38,1.08,0.99,0.89,0.79,0.69,0.59,0.49,0.49,0.49,0.49,0.49,0.49,0.3,0.3,0.3,0.3,0.3,0.2,0.2,0.2,0.2],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Publishers","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}}}
Metrics
Cite this
GOST |
RIS |
BibTex |
MLA
Cite this
GOST
Copy
Hoxhaj G., Manning B. D. The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism // Nature Reviews Cancer. 2019. Vol. 20. No. 2. pp. 74-88.
GOST all authors (up to 50)
Copy
Hoxhaj G., Manning B. D. The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism // Nature Reviews Cancer. 2019. Vol. 20. No. 2. pp. 74-88.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1038/s41568-019-0216-7
UR - https://doi.org/10.1038%2Fs41568-019-0216-7
TI - The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
T2 - Nature Reviews Cancer
AU - Hoxhaj, Gerta
AU - Manning, Brendan D.
PY - 2019
DA - 2019/11/04 00:00:00
PB - Springer Nature
SP - 74-88
IS - 2
VL - 20
PMID - 31686003
SN - 1474-175X
SN - 1474-1768
ER -
Cite this
BibTex
Copy
@article{2019_Hoxhaj,
author = {Gerta Hoxhaj and Brendan D. Manning},
title = {The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism},
journal = {Nature Reviews Cancer},
year = {2019},
volume = {20},
publisher = {Springer Nature},
month = {nov},
url = {https://doi.org/10.1038%2Fs41568-019-0216-7},
number = {2},
pages = {74--88},
doi = {10.1038/s41568-019-0216-7}
}
Cite this
MLA
Copy
Hoxhaj, Gerta, et al. “The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism.” Nature Reviews Cancer, vol. 20, no. 2, Nov. 2019, pp. 74-88. https://doi.org/10.1038%2Fs41568-019-0216-7.