PXD060464

PXD060464 is an original dataset announced via ProteomeXchange.

Title	Targeting chaperone-mediated autophagy inhibits properties of glioblastoma stem cells and restores anti-tumor immunity
Description	Chaperone-mediated autophagy (CMA), a selective autophagic process, plays a crucial role in maintaining intracellular quality and facilitating cellular responses to stress. While CMA has been implicated in finely regulating the stemness of normal stem cells, its significance in cancer stem cells (CSCs) remains largely undefined. In this study, we demonstrate that CMA is upregulated in patient-derived glioblastoma stem cells (GSCs), characterized by a notable increase in the levels of the CMA receptor, lysosome-associated membrane protein type 2A (LAMP2A). The enhanced stability of LAMP2A within GSC lysosomes is a result of MST4-mediated phosphorylation at residues T40, S97, and T136, which facilitates LAMP2A homotrimer formation and diminishes LAMP2A degradation by obstructing the interaction between LAMP2A and Cathepsin A. The contribution of CMA to the self-renewal and tumorigenic potential of GSCs is mediated by the upregulation of mTORC1 activity through the selective lysosomal degradation of its two negative modulators, TSC1 and TSC2. Furthermore, CMA is implicated in promoting resistance to immunotherapy in GBM by inhibiting the TET3-dependent enhancement of tumor cGAS and STING expression. Finally, the genetic or pharmacological inhibition of CMA exhibits a synergistic effect with immune checkpoint therapy in murine models of GBM. Our findings delineate an MST4-LAMP2A signaling pathway that modulates CMA activity and the malignancy of GSCs, with therapeutic targeting of this axis potentially overcoming immunotherapy resistance in GBM.
HostingRepository	PRIDE
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-22_00:55:36.659.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yonghua Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-04 07:35:47	ID requested
⏵ 1	2025-09-22 00:55:37	announced

Dataset with its publication pending

submitter keyword: MST4,Chaperone-mediated autophagy, GSC, LAMP2A, GBM

Tianzhi Huang
contact affiliation	Xiamen University
contact email	huangtianzhi@xmu.edu.cn
lab head
Yonghua Li
contact affiliation	Xiamen University
contact email	21620220157028@stu.xmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060464
     1. Label: PRIDE project
     2. Name: Targeting chaperone-mediated autophagy inhibits properties of glioblastoma stem cells and restores anti-tumor immunity