PXD050295

PXD050295 is an original dataset announced via ProteomeXchange.

Title	Repurposing homoharringtonine for thyroid cancer therapy through TIMP1/FAK/PI3K/AKT signaling pathway
Description	Homoharringtonine (HHT), an alkaloid isolated from Cephalotaxus, is an effective anti-leukemia agent that also exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. This study aimed to explore whether HHT has anti-TC effects and its underlying molecular mechanism. Our findings demonstrated that HHT exhibited strong anti-TC activity, both in vivo and in vitro, that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells following HHT treatment. Overexpression of TIMP1 had the opposite effects of HHT and reversed its inhibitory effects, while TIMP1 downregulation, mimicking the inhibitory effects of HHT, enhanced the anti-TC effects of HHT. Furthermore, the TIMP1 knockdown and rescue experiment revealed that TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted the anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, the FDA-approved drug HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway and be repurposed as a promising agent for TC treatment.
HostingRepository	iProX
AnnounceDate	2024-03-03
AnnouncementXML	Submission_2024-10-17_20:28:00.572.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chuang Xi
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-03 19:46:22	ID requested
1	2024-03-03 19:46:42	announced
⏵ 2	2024-10-17 20:28:01	announced	2024-10-18: Update information.

Xi C, Zhang G, Sun N, Liu M, Ju N, Shen C, Song H, Luo Q, Qiu Z, Repurposing homoharringtonine for thyroid cancer treatment through TIMP1/FAK/PI3K/AKT signaling pathway. iScience, 27(6):109829(2024) [pubmed]

submitter keyword: Thyroid cancer, TIMP1, PI3K/AKT signaling pathway, homoharringtonine

Quanyong Luo
contact affiliation	Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
contact email	luoqy@sjtu.edu.cn
lab head
Chuang Xi
contact affiliation	Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
contact email	chuangxi1019@163.com
dataset submitter

iProX dataset URI