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PXD067033

PXD067033 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Matrix Stiffness-Driven Cytoskeletal Remodeling and Tumor Progression in Anaplastic Thyroid Cancer via Integrin-Focal Adhesion Kinase Signaling
Description	Anaplastic thyroid cancer (ATC) is a highly lethal malignancy characterized by rapid progression and therapeutic resistance. This study uncovers the pivotal role of extracellular matrix (ECM) stiffness in driving ATC aggressiveness through mechanotransduction mediated by the Integrin α6β4/Focal Adhesion Kinase (FAK) axis. By engineering collagen-coated polyacrylamide hydrogels with tunable rigidity, we demonstrated that high ECM stiffness (60 kPa) markedly enhanced ATC cell proliferation, clonogenicity, migration, and invasion. Mechanistically, stiff matrices induced cytoskeletal reorganization, activated RhoA/Rac1/Cdc42 signaling, and upregulated Integrin α6β4-FAK pathway components, as validated by transcriptomic, proteomic, and functional assays. Pharmacological inhibition of FAK reversed stiffness-dependent tumor-promoting effects in vitro. In vivo, mice implanted with high-stiffness ECM-mimicking hydrogels exhibited accelerated subcutaneous tumor growth and increased lung metastatic burden, which were significantly attenuated by FAK-targeted therapy. These findings establish ECM stiffness as a biomechanical determinant of ATC progression and metastasis, offering novel insights into microenvironment-driven malignancy and highlighting FAK as a promising therapeutic target to disrupt mechanosignaling in ATC.
HostingRepository	iProX
AnnounceDate	2025-08-07
AnnouncementXML	Submission_2025-08-07_01:52:44.085.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chenyao Li
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-07 01:52:28	ID requested
⏵ 1	2025-08-07 01:52:44	announced

Publication List

Dataset with its publication pending

Keyword List

submitter keyword: Anaplastic thyroid cancer

Contact List

Guang Chen
contact affiliation	the First Hospital of Jilin University
contact email	chenguang269@163.com
lab head
Chenyao Li
contact affiliation	the First Hospital of Jilin University
contact email	1545559471@qq.com
dataset submitter

Full Dataset Link List

iProX dataset URI