Proteome activity landscapes of tumor cell lines determine drug responses.

Nature Communications
Martin FrejnoBernhard Kuster

Abstract

Integrated analysis of genomes, transcriptomes, proteomes and drug responses of cancer cell lines (CCLs) is an emerging approach to uncover molecular mechanisms of drug action. We extend this paradigm to measuring proteome activity landscapes by acquiring and integrating quantitative data for 10,000 proteins and 55,000 phosphorylation sites (p-sites) from 125 CCLs. These data are used to contextualize proteins and p-sites and predict drug sensitivity. For example, we find that Progesterone Receptor (PGR) phosphorylation is associated with sensitivity to drugs modulating estrogen signaling such as Raloxifene. We also demonstrate that Adenylate kinase isoenzyme 1 (AK1) inactivates antimetabolites like Cytarabine. Consequently, high AK1 levels correlate with poor survival of Cytarabine-treated acute myeloid leukemia patients, qualifying AK1 as a patient stratification marker and possibly as a drug target. We provide an interactive web application termed ATLANTiC (http://atlantic.proteomics.wzw.tum.de), which enables the community to explore the thousands of novel functional associations generated by this work.

References

Dec 29, 1988·The New England Journal of Medicine·UNKNOWN Early Breast Cancer Trialists' Collaborative Group
Jun 7, 1996·The Journal of Biological Chemistry·G S TakimotoK B Horwitz
Jun 29, 2000·Oncogene·A FollenziP M Comoglio
Dec 31, 2005·Genes & Development·David KashatusAlbert S Baldwin
Apr 14, 2006·Nature Reviews. Molecular Cell Biology·Josef Jiricny
May 31, 2007·European Journal of Human Genetics : EJHG·Aster Alemayehu, Ivana Fridrichova
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
May 4, 2010·Nature·Johanna C ScheuermannJürg Müller
May 10, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski
Jan 18, 2013·BMC Bioinformatics·Sonja HänzelmannJustin Guinney
Feb 19, 2013·The International Journal of Biochemistry & Cell Biology·Marjan AmiriNicola Solaroli
Aug 2, 2013·Science Translational Medicine·Ryan B CorcoranJeffrey A Engelman
Aug 13, 2013·Cell Reports·Amin Moghaddas GholamiBernhard Kuster
Feb 28, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shakun M MalikRichard Pazdur
Jun 3, 2014·BMC Bioinformatics·Chen MengAmin Moghaddas Gholami
Apr 22, 2015·Cell Reports·Robert T LawrenceJudit Villén
Nov 4, 2015·Nucleic Acids Research·Juan Antonio VizcaínoHenning Hermjakob
Jun 3, 2016·Nature·Philipp MertinsUNKNOWN NCI CPTAC
Jul 12, 2016·Cell·Francesco IorioMathew J Garnett
Sep 13, 2016·Oncogene·T ZhanM Boutros
Dec 20, 2016·Nature Medicine·Constanze SchneiderJindrich Cinatl
Aug 31, 2017·Cell Reports·Theodoros I RoumeliotisJyoti S Choudhary
Nov 5, 2017·Molecular Systems Biology·Martin FrejnoBernhard Kuster
Nov 7, 2017·Nucleic Acids Research·Tobias SchmidtMathias Wilhelm
Dec 2, 2017·Science·Susan KlaegerBernhard Kuster
Feb 6, 2018·Molecular Cell·Junko MuraiYves Pommier

❮ Previous
Next ❯

Citations

Apr 21, 2021·Expert Review of Proteomics·Olson Tsang, Jason W H Wong
May 11, 2021·Briefings in Bioinformatics·Florian BorchertMatthieu-P Schapranow
Jun 8, 2021·Molecular Therapy Oncolytics·Xiao-Li YangDa Fu
Jul 8, 2021·Chemical Reviews·Juan D ChavezJames E Bruce
Sep 2, 2021·Expert Review of Proteomics·Jacqueline S Gerritsen, Forest M White

❮ Previous
Next ❯

Methods Mentioned

BETA
deubiquitination

Software Mentioned

ATLANTiC
PRIDE

Related Concepts

Related Feeds

Acute Myeloid Leukaemia & RNA

Acute myeloid leukaemia (AML) is a common hematological type of cancer. As the population ages, there has been a rise in the frequency of AML. RNA expression has been used to see if there are different genetic profiles that exist within AML and whether these may underpin the variations in survival rates. Here is the latest research on AML and RNA.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.