PXD026078

PXD026078 is an original dataset announced via ProteomeXchange.

Title	Impaired stability of tumor cells after targeting of lactate/pyruvate metabolism investigated by shotgun proteomics
Description	Overexpression of heat shock proteins (HSPs), especially the major stress-inducible 72 kDa heat shock protein 70 (Hsp70), in malignant tumor cells is associated with therapeutic resistance. The heightened metabolic demand in tumor cells (Warburg effect) increases lactate dehydrogenase (LDH) activity and the corresponding increase in lactate concentrations promotes malignancy. Herein, we assessed the co-regulation of LDH and the heat shock response and its link to radiation resistance in B16F10 murine melanoma cells and LS174T human colorectal adenocarcinoma cells. Inhibition of LDHA/B by oxamate or GNE-140, significantly diminishes the expression of Hsp90, Hsp70 and Hsp27 in the cytosol. Diminished expression was also observed in LDHA/B double knockout (LDH-/-) cells. An increased production of reactive oxygen species (ROS) induced by a faster growth rate in wild type (WT) vs LDH-/- cells contributes to increased cytosolic HSP levels in WT cells. LDH-/- cells exhibit a lower density of membrane Hsp70 expression than WT cells and a decreased presence of the tumor-specific, Hsp70 anchoring glycosphingolipid Gb3 on the cell surface which could be attributed to an altered lipid metabolism mediated by the LDH knockout. Functionally, a double knockout of LDHA/B results in a generalized reduction in expression of HSPs in tumor cells and significantly increases radiosensitivity which is associated with a G2/M arrest. In summary, we demonstrate that pharmacological targeting of the lactate/pyruvate metabolism breaks radioresistance by impairing the stress response.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_03:49:15.430.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine von Toerne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-18 06:53:03	ID requested
⏵ 1	2022-02-17 03:49:16	announced

Schwab M, Thunborg K, Azimzadeh O, von Toerne C, Werner C, Shevtsov M, Di Genio T, Zdralevic M, Pouyssegur J, Renner K, Kreutz M, Multhoff G, Targeting Cancer Metabolism Breaks Radioresistance by Impairing the Stress Response. Cancers (Basel), 13(15):(2021) [pubmed]

submitter keyword: LDHA/B double knockout, lactate/pyruvate metabolism, heat shock proteins, radiosensitivity, membrane Hsp70 expression, LC-MSMS

Gabriele Multhoff
contact affiliation	Central Institute for Translational Cancer Research (TranslaTUM) Radiation Immuno-Oncology Group, Klinikum rechts der Isar
contact email	gabriele.multhoff@tum.de
lab head
Christine von Toerne
contact affiliation	Helmholtz Zentrum München
contact email	vontoerne@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD026078

PRIDE project URI

• PRIDE
  1. PXD026078
     1. Label: PRIDE project
     2. Name: Impaired stability of tumor cells after targeting of lactate/pyruvate metabolism investigated by shotgun proteomics