PXD056884-1

PXD056884 is an original dataset announced via ProteomeXchange.

Title	Carbonic anhydrase 2 facilitates sorafenib resistance by counteracting MCT4-mediated intracellular pH dysregulation in hepatocellular carcinoma
Description	Sorafenib, the first targeted therapy for hepatocellular carcinoma (HCC), has been utilized in clinics over a decade. However, its effectiveness is severely hindered by the acquired drug resistance, the mechanisms of which remain largely elusive. In this study, we identify that carbonic anhydrase 2 (CA2) is a key regulator of sorafenib resistance. Mechanistically, sorafenib treatment decreases intracellular pH (pHi) by suppressing monocarboxylate transporter 4 (MCT4) expression, while high levels of CA2 counteract MCT4-mediated pHi dysregulation upon sorafenib treatment, maintaining pHi homeostasis to facilitate cell survival and sorafenib resistance. Targeting CA2 re-sensitizes resistant HCC cells to sorafenib both in vitro and in vivo. Importantly, analysis of clinical samples demonstrates a strong correlation between CA2 expression levels and the therapeutic efficacy of sorafenib in HCC patients. Our findings highlight the significance of CA2 in facilitating sorafenib resistance and propose targeting CA2 as a potential strategy for overcoming sorafenib resistance in HCC patients.
HostingRepository	PRIDE
AnnounceDate	2024-10-24
AnnouncementXML	Submission_2024-10-23_20:02:43.226.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hui Lu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 23:46:03	ID requested
⏵ 1	2024-10-23 20:02:43	announced

Dataset with its publication pending

submitter keyword: sorafenib resistance,Hepatocellular carcinoma,HCC organoids

Huafeng Zhang
contact affiliation	University of Science and Technology of China
contact email	hzhang22@ustc.edu.cn
lab head
Hui Lu
contact affiliation	university of science and technology of china
contact email	luhui941230@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056884
     1. Label: PRIDE project
     2. Name: Carbonic anhydrase 2 facilitates sorafenib resistance by counteracting MCT4-mediated intracellular pH dysregulation in hepatocellular carcinoma