PXD032025-1

PXD032025 is an original dataset announced via ProteomeXchange.

Title	Stromal Changes in The Aged Lung Induce an Emergence From Melanoma Dormancy
Description	Disseminated cancer cells (DCCs) that escape the primary site can seed in distal tissues, but may take several years, or even decades to grow out into overt metastases, a phenomenon termed tumor dormancy. Despite its importance in metastasis and residual disease, few studies have been able to successfully model or characterize dormancy within melanoma. Here, we show that age-related changes in the lung microenvironment facilitate a permissive niche for efficient outgrowth of disseminated dormant tumor cells, in contrast to the aged skin, where age-related changes suppress melanoma growth but drive dissemination. A model of melanoma progression that addresses these microenvironmental complexities is the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1-3. We have previously shown that dermal fibroblasts are key orchestrators of promoting phenotype switching in primary melanoma tumors via changes in the secretion of soluble factors during aging4-8. Our new data identifies Wnt5A as a master regulator of activating melanoma DCC dormancy within the lung, which initially enables efficient dissemination and seeding of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble Wnt antagonist sFRP1, which inhibits Wnt5A, enabling efficient metastatic outgrowth. Further, we have identified the tyrosine kinase receptors AXL and MER as promoting a dormancy-toreactivation axis respectively. Overall, we find that age-induced changes in distal metastatic microenvironments promotes efficient reactivation of dormant melanoma cells in the lung.
HostingRepository	MassIVE
AnnounceDate	2022-06-10
AnnouncementXML	Submission_2022-06-10_13:58:32.906.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hsin-Yao Tang
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Carbamidomethyl; unknown modification
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-03 07:43:44	ID requested
⏵ 1	2022-06-10 13:58:33	announced

Fane ME, Chhabra Y, Alicea GM, Maranto DA, Douglass SM, Webster MR, Rebecca VW, Marino GE, Almeida F, Ecker BL, Zabransky DJ, H, ü, ser L, Beer T, Tang HY, Kossenkov A, Herlyn M, Speicher DW, Xu W, Xu X, Jaffee EM, Aguirre-Ghiso JA, Weeraratna AT, Stromal changes in the aged lung induce an emergence from melanoma dormancy. Nature, 606(7913):396-405(2022) [pubmed]

submitter keyword: TMT10plex, Melanoma, Aged Lung

Ashani T. Weeraratna
contact affiliation	Johns Hopkins Bloomberg School of Public Health
contact email	aweeraratna@jhu.edu
lab head
Hsin-Yao Tang
contact affiliation	The Wistar Institute
contact email	tangh@wistar.org
dataset submitter

MassIVE dataset URI

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