PXD025389

PXD025389 is an original dataset announced via ProteomeXchange.

Title	Activation of CD44 / AKT signaling promotes resistance to FGFR1 inhibition in squamous cell lung cancer
Description	Lung cancer is the leading cause of cancer related deaths, worldwide. Fibroblast growth factor receptor 1 (FGFR1) gene amplification is one of the most prominent and potentially targetable genetic alterations in squamous cell lung cancer (SQCLC). Highly selective tyrosine kinase inhibitors have been developed to target FGFR1, however, resistance mechanisms originally existing in patients or acquired throughout treatment have limited treatment efficiency in clinical trials, so far. In this study, we performed a wide-scale phosphoproteomic mass spectrometry analysis to explore signaling pathways that lead to FGFR1 inhibition resistance in lung cancer cells with intrinsic, induced and mutational resistance. We identified a CD44/AKT signaling axis as a new and common mechanism of resistance to FGFR1 inhibition in lung cancer. Co-inhibition of AKT or CD44 synergistically sensitized intrinsic and induced resistant cells to FGFR1 inhibition. Furthermore, strong CD44 expression was significantly correlated to AKT activation in squamous cell lung cancer patients. Collectively, our phosphoproteomic analysis of FGFR1 inhibitor resistant lung cancer cells promotes a large data library of resistance associated phosphorylation patterns and proposes a common resistance pathway consisting of CD44 and AKT activation. Examination of CD44/AKT activation could help to predict response to FGFR1 inhibition and combination with AKT inhibitors might path the way for an effective therapy of FGFR1 dependent lung cancer patients in case of treatment resistance.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_01:16:11.460.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hanibal Bohnenberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-14 02:08:33	ID requested
⏵ 1	2022-08-12 01:16:12	announced

Elakad O, H, ä, upl B, Labitzky V, Yao S, K, ü, ffer S, von Hammerstein-Equord A, Danner BC, J, ü, cker M, Urlaub H, Lange T, Str, ö, bel P, Oellerich T, Bohnenberger H, Activation of CD44/PAK1/AKT signaling promotes resistance to FGFR1 inhibition in squamous-cell lung cancer. NPJ Precis Oncol, 6(1):52(2022) [pubmed]

submitter keyword: FGFR1, AKT, CD44, lung cancer, mass spectrometry, phosphoproteomics

Hanibal Bohnenberger
contact affiliation	Institute of Pathology University Medical Center Robert-Koch-Str. 40 37075 Goettingen Germany
contact email	Hanibal.bohnenberger@med.uni-goettingen.de
lab head
Hanibal Bohnenberger
contact affiliation	University medical center Goettingen, Institute of Pathology
contact email	hanibal.bohnenberger@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025389
     1. Label: PRIDE project
     2. Name: Activation of CD44 / AKT signaling promotes resistance to FGFR1 inhibition in squamous cell lung cancer