The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.

Cancer Cell
Milica MomcilovicDavid B Shackelford

Abstract

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.

References

Oct 18, 2003·The Journal of Biological Chemistry·Mark A GregoryStephen R Hann
Dec 3, 2003·Molecular Imaging·Andreas Markus Loening, Sanjiv Sam Gambhir
Jan 27, 2004·The American Journal of Pathology·Kyung U HongBarry R Stripp
Dec 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Emma L RawlinsBrigid L M Hogan
Jul 7, 2007·Cancer Cell·David A Guertin, David M Sabatini
Aug 7, 2007·Nature·Hongbin JiKwok-Kin Wong
Jan 2, 2008·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Thierry BerghmansUNKNOWN European Lung Cancer Working Party for the IASLC Lung Cancer Staging Project
Oct 25, 2008·Nature·Li DingRichard K Wilson
Sep 16, 2009·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Daniel MorgenszternRamaswamy Govindan
Nov 20, 2009·Cell Cycle·Chong XuBarry M Gumbiner
Sep 23, 2011·Pediatric Hematology and Oncology·Franziska WalterJohannes Czernin
Nov 22, 2011·Nature·Andrew R MullenRalph J DeBerardinis
Nov 22, 2011·Nature·Christian M MetalloGregory Stephanopoulos
Dec 6, 2011·Cancer Discovery·Vanessa S Rodrik-OutmezguineNeal Rosen
Sep 11, 2012·Nature·UNKNOWN Cancer Genome Atlas Research Network
Dec 6, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mohamed HassaneinPierre P Massion
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Jan 22, 2015·The Journal of Clinical Investigation·Katherine SellersTeresa W-M Fan
Feb 13, 2015·Science Translational Medicine·Sriram VennetiCraig B Thompson
May 15, 2015·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Mohamed HassaneinH Charles Manning
Jun 2, 2015·The New England Journal of Medicine·Julie BrahmerDavid R Spigel
Nov 18, 2015·Cancer Research·Milica MomcilovicDavid B Shackelford
Feb 9, 2016·Cell·Christopher T HensleyRalph J DeBerardinis
Feb 9, 2016·Cell Metabolism·Shawn M DavidsonMatthew G Vander Heiden
Jan 19, 2017·Cell Reports·Milica MomcilovicDavid B Shackelford
Dec 6, 2017·Scientific Reports·Peter BankheadPeter W Hamilton

❮ Previous
Next ❯

Citations

Mar 31, 2019·Expert Review of Proteomics·Yao AnCanhua Huang
Apr 4, 2019·American Journal of Respiratory Cell and Molecular Biology·Huachun CuiGang Liu
May 1, 2019·American Journal of Respiratory Cell and Molecular Biology·Vincent Esguerra, Yutong Zhao
Nov 2, 2019·Nature·Milica MomcilovicDavid B Shackelford
Dec 11, 2019·Cells·Cedric MagawayEstela Jacinto
Mar 5, 2020·Nature Reviews. Endocrinology·Benjamin D HopkinsLewis C Cantley
Jul 3, 2020·Cancer Biotherapy & Radiopharmaceuticals·Shu-Ping HuangTing-Qing Gan
Jul 7, 2019·Journal of Hematology & Oncology·Hui HuaYangfu Jiang
Jan 28, 2020·Human Molecular Genetics·Alessandra MarescaValerio Carelli
Nov 15, 2018·Nature Reviews. Cancer·Dirk MossmannMichael N Hall
Dec 18, 2018·International Journal of Radiation Biology·Gunnar BoysenRobert J Griffin
Jul 23, 2020·Nature Metabolism·Andrés Méndez-LucasMariia Yuneva
Mar 28, 2020·Nature·Naama KanarekDavid M Sabatini
Oct 2, 2020·Cancers·Atsushi Tanabe, Hiroeki Sahara
Jun 11, 2020·Cancers·Mariacarmela SantarpiaRafael Rosell
Nov 2, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Catríona M DowlingKwok-Kin Wong
Nov 29, 2020·Current Opinion in Biotechnology·Nina C FlerinMassimiliano Mazzone
Oct 2, 2019·Cancer Letters·José M MatésJavier Márquez
Nov 2, 2019·Molecular Metabolism·Peter KreuzalerMariia Yuneva
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Geetha Venkateswaran, Shoukat Dedhar
Dec 20, 2020·Cancers·Pasquale SaggeseClaudio Scafoglio
Feb 19, 2021·Physiological Reviews·Angelia SzwedEstela Jacinto
May 1, 2019·Current Medicinal Chemistry·José M MatésJavier Márquez
Feb 21, 2021·Cell Metabolism·Abigail S KrallHeather R Christofk
Nov 5, 2020·Archives of Biochemistry and Biophysics·Tao YuXiongbin Lu
Mar 5, 2021·Pharmacology & Therapeutics·Lingfan LiangZeping Hu
Mar 13, 2021·Oncogene·Yuanwang PanKwok-Kin Wong

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.