You are not logged in.
Openly accessible

Proteomic identification of the lactate dehydrogenase A in a radioresistant prostate cancer xenograft mouse model for improving radiotherapy

Hao, Jingli, Graham, Peter, Chang, Lei, Ni, Jie, Wasinger, Valerie, Beretov, Julia, Deng, Junli, Duan, Wei, Bucci, Joseph, Malouf, David, Gillatt, David and Li, Yong 2016, Proteomic identification of the lactate dehydrogenase A in a radioresistant prostate cancer xenograft mouse model for improving radiotherapy, Oncotarget, vol. 7, no. 45, pp. 74269-74285, doi: 10.18632/oncotarget.12368.

Attached Files
Name Description MIMEType Size Downloads
duan-proteomicidentification-2017.pdf Published version application/pdf 4.97MB 8

Title Proteomic identification of the lactate dehydrogenase A in a radioresistant prostate cancer xenograft mouse model for improving radiotherapy
Author(s) Hao, Jingli
Graham, Peter
Chang, Lei
Ni, Jie
Wasinger, Valerie
Beretov, Julia
Deng, Junli
Duan, Wei
Bucci, Joseph
Malouf, David
Gillatt, David
Li, Yong
Journal name Oncotarget
Volume number 7
Issue number 45
Start page 74269
End page 74285
Total pages 17
Publisher Impact Journals LLC
Place of publication Albany, N.Y.
Publication date 2016-09-30
ISSN 1949-2553
Keyword(s) LDHA
glycolysis
prostate cancer
proteomics
radiotherapy
Summary Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry. One selected glycolysis marker, lactate dehydrogenase A (LDHA) was validated, and further investigated for its role in CaP radioresistance. We found that 378 proteins and 51 pathways were significantly differentially expressed between PC-3RR and PC-3 xenograft tumors, and that the glycolysis pathway is closely linked with CaP radioresistance. In addition, we also demonstrated that knock down of LDHA with siRNA or inhibition of LDHA activity with a LDHA specific inhibitor (FX-11), could sensitize PC-3RR cells to radiotherapy with reduced epithelial-mesenchymal transition, hypoxia, DNA repair ability and autophagy, as well as increased DNA double strand breaks and apoptosis. In summary, we identified a list of potential RR protein markers and important signaling pathways from a PC-3RR xenograft mouse model, and demonstrate that targeting LDHA combined with radiotherapy could increase radiosensitivity in RR CaP cells, suggesting that LDHA is an ideal therapeutic target to develop combination therapy for overcoming CaP radioresistance.
Language eng
DOI 10.18632/oncotarget.12368
Field of Research 111208 Radiation Therapy
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30091752

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in TR Web of Science
Scopus Citation Count Cited 1 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 45 Abstract Views, 9 File Downloads  -  Detailed Statistics
Created: Tue, 07 Mar 2017, 09:59:05 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.