PXD023207

PXD023207 is an original dataset announced via ProteomeXchange.

Title	Identification of Pimavanserin tartrate as a Potent Ca2+-Calcineurin-NFAT Pathway Inhibitor for Glioblastoma Therapy
Description	Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumor. Although alkylating agents (such as temozolomide (TMZ)) are widely used as first-line treatments for GBM, they often cause chemoresistance and are poorly effective for recurrent GBM. Therefore, anti-GBM drugs with novel mechanism are urgently needed clinically. Here, we report an effective Ca2 +-calcineurin-NFAT signaling pathway inhibitor (Pimavanserin), which exhibits effective anti-tumor activity against GBM. Pimavanserin induces GBM cell cycle arrest in G1/S, promotes cell apoptosis and inhibits tumor cell proliferation and metastasis. Through an in-depth study of the mechanism, it is found that Pimavanserin eliminates NFAT nuclear translocation by inhibiting the formation of puncta of STIM1. Subsequent transcriptomic and proteomic analysis unveiled that PIM can down-regulate E2F, MYC ATR and AuroraA/B signaling pathways to inhibit GBM cancer growth both in vitro and in vivo. In addition, the upregulated genes were mainly associated with cholesterol homeostasis and fatty acid synthesis, which may underlie the mechanism of PIM’s phospholipidosis side effect. This article is the first report of Pimavanserin as an anti- GBM drug.
HostingRepository	iProX
AnnounceDate	2020-12-17
AnnouncementXML	Submission_2023-02-21_18:30:28.118.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhenzhen Liu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-17 17:20:37	ID requested
1	2021-06-03 23:28:51	announced
⏵ 2	2023-02-21 18:30:29	announced	2023-02-22: Update publication information.

Liu ZZ, Liu XN, Fan RC, Jia YP, Zhang QK, Gao XQ, Wang YQ, Yang MQ, Ji LZ, Zhou YQ, Li HL, Li P, Tang B, -calcineurin-NFAT pathway inhibitor for glioblastoma therapy. Acta Pharmacol Sin, 42(11):1860-1874(2021) [pubmed]

submitter keyword: Glioblastoma multiforme，Pimavanserin

Ping Li
contact affiliation	Shandong Normal University
contact email	lip@sdnu.edu.cn
lab head
Zhenzhen Liu
contact affiliation	Shandong Normal University
contact email	liuzhenzhen87@126.com
dataset submitter

iProX dataset URI