PXD038916-1

PXD038916 is an original dataset announced via ProteomeXchange.

Title	Spry1 as a potential new hypoxia modulator in cutaneous melanoma
Description	Introduction. At present, the precise role of Spry proteins in tumor progression is still debated. Our previous study showed that Spry1 knockdown (Spry1KO) in BRAFV600-mutant cutaneous melanoma (CM) promoted cell cycle arrest and apoptosis, repressed cell proliferation in vitro, and reduced tumor growth in vivo. Furthermore, we observed that Spry1 loss impaired angiogenesis in vivo. Hypoxia has been recognized as one of the crucial features of CM. Hypoxia results in the activation of the transcription factor hypoxia-inducible factor 1α (HIF‐1α), which represents a master regulator of angiogenesis. Hence, the present study was designed to explore a possible role of Spry1 in modulating angiogenesis and hypoxia in CM. Materials and methods. SPRY1 gene was knocked-out using the CRISPR strategy in the BRAF wild-type (wt) Mel 313 and in the BRAF-mutant Mel 593 cell lines. Angiogenic potential was assessed through in vivo CD31 staining and in vitro tube formation assays. By using in vitro and in vivo models, the effects of Spry1KO on hypoxia-related genes were investigated through RNA-sequencing (RNA-seq), quantitative real-time PCR, western blot, and immunofluorescence analyses. To gain insight into Spry1 interactome, immunoprecipitation coupled to mass spectrometry (IP-MS) was employed. Results and discussion. Consistent with our previous data, tumors arising from Mel 313 and Mel 593 Spry1KO clones were significantly smaller than those from their corresponding parental cells. Tumor growth inhibition was accompanied by a substantial reduction of angiogenesis, as assessed by the immunofluorescence staining of CD31 in vivo and the tube formation assay in vitro. Accordingly, RNA-seq analysis indicated that the vascular endothelial growth factor A was significantly down-regulated following Spry1 silencing. Notably, Ingenuity Pathway Analysis identified “HIF-1α Signaling” as the most significant molecular and cellular function affected in vivo by Spry1 silencing regardless of the BRAF mutational status. Analyses of tumor tissues confirmed that Spry1KO significantly reduced HIF1-α protein abundance. Interestingly, HIF-1α mRNA levels were minimally affected, thus suggesting that Spry1KO might impact on HIF-1α expression post-translationally. IP-MS identified about 50 Spry1 protein partners, and most of them were mitochondrial. Importantly, western blot analysis of cytosolic and mitochondrial proteins revealed that Spry1 was largely expressed in CM cell lines irrespective of BRAF mutation. Conclusions. Altogether, these data lead us to speculate that Spry1 might play a role in mitochondria homeostasis, thus impacting on hypoxia and angiogenesis in CM.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:56:56.748.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tuula Nyman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF fleX

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-19 03:21:28	ID requested
⏵ 1	2025-05-06 09:56:57	announced

10.1186/s13046-025-03289-8;

Montico B, Giurato G, Guerrieri R, Colizzi F, Salvati A, Nassa G, Lamberti J, Memoli D, Sabatelli P, Comelli M, Bellazzo A, Fejza A, Camicia L, Baboci L, Dal Bo M, Covre A, Nyman TA, Weisz A, Steffan A, Maio M, Sigalotti L, Mongiat M, Andreuzzi E, Fratta E, -dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma. J Exp Clin Cancer Res, 44(1):53(2025) [pubmed]

submitter keyword: Cutaneous melanoma, hypoxia, BRAF, IP-MS, Spry1

Tuula Nyman
contact affiliation	Head of Proteomics
contact email	tuula.nyman@medisin.uio.no
lab head
Tuula Nyman
contact affiliation	University of Oslo
contact email	tuula.nyman@medisin.uio.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038916
     1. Label: PRIDE project
     2. Name: Spry1 as a potential new hypoxia modulator in cutaneous melanoma