ATLANTIC: Activity landscapes of tumor cell lines determine drug responses

ABSTRACT: Analysis of cancer cell line (CCL) genomes, proteomes and phenotypic drug responses are emerging approaches to uncover molecular mechanisms of drug action. We extended this paradigm to measuring proteome activity landscapes by integrating quantitative data for 10,000 proteins and 55,000 phosphorylation sites from 125 CCLs with large drug sensitivity data collections. To engage the scientific community in mining the thousands of novel functional associations generated by this work, we provide an interactive web resource termed ATLANTIC (http://atlantic.proteomics.wzw.tum.de). For instance, we found that Progesterone Receptor (PGR) phosphorylation is a stronger drug response predictor than PGR expression alone in hormone receptor positive breast cancer patients. We also demonstrate that Adenylate kinase isoenzyme 1 (AK1) inactivates chemotherapeutic drugs such as Cytarabine. Consequently, high AK1 levels correlated with poor survival of Cytarabine-treated acute myelogenous leukemia patients qualifying AK1 as a treatment stratification and drug response marker and possibly as a drug target.

INSTRUMENT(S): LTQ Orbitrap Velos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Lung Cancer,Leukemia,Colon Cancer,Melanoma,Prostate Cancer,Brain Cancer,Kidney Cancer,Malignant Neoplasm Of Ovary,Breast Cancer

SUBMITTER: Martin Frejno  

LAB HEAD: Bernhard Kuster

PROVIDER: PXD013615 | Pride | 2020-07-27

REPOSITORIES: Pride