PXD021307-2

PXD021307 is an original dataset announced via ProteomeXchange.

Title	FER drives tumor progression cues of invasive breast cancer cells through kinase-dependent control of proliferation and endosomal recycling
Description	Triple-Negative Breast Cancer (TNBC) is a poorly targetable cancer subtype that exhibits a high metastatic potential. To develop new intervention strategies, it is crucial to understand the mechanisms governing migratory and invasive features of TNBC cells. Previously it was shown that high expression of the non-receptor tyrosine kinase FER is an independent prognostic factor that correlates with poor survival in high grade and basal breast cancer. Here, we show that FER controls proliferation and invasion of TNBC cells through the direct substrates MAPK1 and Dynactin 2 (DCTN2; Dynamitin). Our data demonstrate that FER regulates tumor cell proliferation through phosphorylation of MAPK1 on tyrosine 187, and recycling endosome function and subsequent invasion of breast cancer cells through tyrosine 6 residue (Y6) of DCTN2. We show that DCTN2-Y6 is essential for Dynein complex formation and the development of tubular recycling domains at the early endosome. By controlling this crucial step in endosomal recycling, FER drives and sustains adhesion and invasion of (triple negative) breast cancer cells. Our data provide clinical ramification by demonstrating that high grade and basal breast cancers expressing elevated FER levels are more susceptible to taxane-based chemotherapy interventions. In conclusion, our study links FER to kinase-dependent control of intracellular vesicular transport and tumor progression in breast cancer. Importantly, our results indicate that FER represents a predictive and functional biomarker in high grade basal breast cancers.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:51:37.161.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-04 02:50:17	ID requested
1	2022-04-15 05:11:41	announced
⏵ 2	2023-11-14 08:51:37	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: analogue-sensitive, cell invasion, endosomal recycling.,Breast cancer, FER tyrosine kinase, proliferation

Patrick W.B. Derksen
contact affiliation	Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
contact email	P.W.B.Derksen@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021307
     1. Label: PRIDE project
     2. Name: FER drives tumor progression cues of invasive breast cancer cells through kinase-dependent control of proliferation and endosomal recycling