Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics

Li, Qingdi Quentin; Hao, Jun; Zhang, Zheng; Krane, L. Spencer; Hammerich, Kai; Sanford, Thomas; Trepel, Jane B.; Neckers, Len; Agarwal, Piyush K.

doi:10.1038/s41598-017-00143-6

Cited by 47 publications

(51 citation statements)

References 53 publications

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“…As a result of the absence of H4K20me3 has been positively correlated with the development of cancers (Pogribny et al, 2007[ 22 ]; Balakrishnan and Milavetz, 2010[ 1 ]). In the present study, the H4K20me3 level increased following the low-/high-dose GA treatment for 6 h and low-dose 17-DMAG for 6 h, whereas it decreased in the cells treated with GA and 17-DMAG for 24 h. Our results are consistent with those of Li et al (2017[ 19 ]). They demonstrated that H4K20me3 and H4K12ac levels increased in a 5637 bladder cancer cell line following treatment with HSP90 inhibitors (AUY922, STAT9090, and SNX-2112).…”

Section: Discussionsupporting

confidence: 93%

The effect of heat shock protein 90 inhibitors on histone 4 lysine 20 methylation in bladder cancer

Çoban

Varol

2019

EXCLI Journal; 18:Doc195; ISSN 1611-2156

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Section: Discussionsupporting

confidence: 93%

The effect of heat shock protein 90 inhibitors on histone 4 lysine 20 methylation in bladder cancer

Çoban

Varol

2019

EXCLI Journal; 18:Doc195; ISSN 1611-2156

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“…Epigenetic modifying drugs display substantially modified potency depending on cellular HDJ2 status. While previous studies have indicated the association between proteomic changes and histone PTMs in response to Hsp90 inhibitor treatment in bladder carcinoma cells, no such association has been shown for HDJ2 and Histone PTMs [64]. Interestingly, vorinostat was the only drug that was synergistic to HDJ2 inhibition.…”

Section: Discussionmentioning

confidence: 90%

Chemogenomic screening Identifies the Hsp70 Co-chaperone HDJ2 as a Hub for Anticancer Drug Resistance

Nitika

Blackman

Knighton

et al. 2019

Preprint

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24Heat shock protein 70 (Hsp70) is an important molecular chaperone that regulates 25 oncoprotein stability and tumorigenesis. However, attempts to develop anti-chaperone 26 drugs targeting molecules such as Hsp70 have been hampered by toxicity issues. Hsp70 27 is regulated by a suite of co-chaperone molecules that bring "clients" to the primary 28 chaperone for efficient folding. Therefore, rather than targeting Hsp70 itself, here we have 29 examined the feasibility of inhibiting the co-chaperone HDJ2, a member of the J domain 30 protein family, as a novel anticancer strategy. We found HDJ2 to be upregulated in a 31 variety of cancers, suggesting a role in malignancy. To confirm this role, we screened the 32 NIH Approved Oncology collection for chemical-genetic interactions with loss of HDJ2 in 33 cancer. 41 compounds showed strong synergy with HDJ2 loss, whereas 18 dramatically 34 lost potency. Several of these hits were validated using a HDJ2 inhibitor (116-9e) in 35 castration-resistant prostate cancer cell (CRPC) and spheroid models. Taken together, 36 these results confirmed that HDJ2 is a hub for anticancer drug resistance and that HDJ2 37 inhibition may be a potent strategy to sensitize cancer cells to current and future 38 therapeutics. 39 40 41 42 104 Materials and Methods 105 Cell culture. The HAP1 Chronic Myelogenous Leukemia cancer cell line and HDJ2 106 Knockout cell line was purchased from Horizon Discovery and were cultured in Iscove's 107 Modified Eagle Medium (Invitrogen) with 10% fetal bovine serum (Gibco), 100 units/ml 108 penicillin, and 100 μg/ml streptomycin at 5% CO2 and 37° C. The LNCaP cancer cell line 109 was purchased from ATCC and were cultured in RPMI-1640 medium (Invitrogen) with 110 10% fetal bovine serum (FBS, Clontech), 100 units/ml penicillin, and 100 μg/ml 111 streptomycin at 5% CO2 and 37° C. 112 6 Drug Screening. Approved Oncology Drug plates consisting of the most current FDA 113 approved anticancer drugs were obtained from National Cancer Institute (NCI). For 114 experiments delineating the synergy between the loss of HDJ2 and approved anticancer 115 drug, HAP1 cells and HAP1 (HDJ2 KO) cells were plated in growth media at 20% 116 confluency 1 day prior to drug treatment. On Day 1 of treatment, cells were treated with 117 DMSO (control), Approved oncology anticancer drugs at 50 µM for 72 hours. Following 118 drug treatments, Cell Titer-Glo reagent was added directly to the wells according to 119 manufacturer's instructions. The luminescence was measured on Bio-Tek Plate reader. 120 Luminescence reading was normalized to and expressed as a relative percentage of the 121 plate averaged DMSO control. The data shown are the mean and SEM of three 122 independent biological replicates. 123 Combination index (CI) calculations. For IC50 calculations, LNCaP cells were seeded 124 in triplicates in 96-well white bottom Nunc plates in growth media at 20% confluency 1 day 125 prior to initiation of drug treatment. On Day 1 of treatment, cells were treated with DMSO 126 (control) and ten ...

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“…Proteome analysis has been used to study the effects and molecular mechanisms of novel potential drugs for BC. Using the 5637 urinary BC cell line, Li et al [ 62 ] evaluated the effect of five heat shock protein 90 (HSP90) inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) in vitro , followed by quantitative proteome analysis at the global and histone post-translational modification levels. HSP90 inhibitors suppress cell proliferation and growth in a dose and time-dependent manner.…”

Section: Applying Proteomics To Bc Researchmentioning

confidence: 99%

Proteomic profiling of bladder cancer for precision medicine in the clinical setting: A review for the busy urologist

et al. 2020

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At present, proteomic methods have successfully identified potential biomarkers of urological malignancies, such as prostate cancer (PC), bladder cancer (BC), and renal cell carcinoma (RCC), reflecting different numbers of key cellular processes, including extracellular environment modification, invasion and metastasis, chemotaxis, differentiation, metabolite transport, and apoptosis. The potential application of proteomics in the detection of clinical markers of urological malignancies can help improve patient assessment through early cancer detection, prognosis, and treatment response prediction. A variety of proteomic studies have already been carried out to find prognostic BC biomarkers, and a large number of potential biomarkers have been reported. It is worth noting that proteomics research has not been applied to the study of predictive markers; this may be due to the incompatibility between the number of measured variables and the available sample size, which has become particularly evident in the study of therapeutic response. On the contrary, prognostic correlation is more common, which is also reflected in existing research. We are now entering an era of clinical proteomics. Driven by proteomic-based workflows, computing tools, and the applicability of cross-correlation of proteomic data, it is now feasible to use proteomic analysis to support personalized medicine. In this paper, we will summarize the current emerging technologies for advanced discovery, targeted proteomics, and proteomic applications in BC, particularly in discovery of human-based biomarkers.

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Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics

Cited by 47 publications

References 53 publications

The effect of heat shock protein 90 inhibitors on histone 4 lysine 20 methylation in bladder cancer

The effect of heat shock protein 90 inhibitors on histone 4 lysine 20 methylation in bladder cancer

Chemogenomic screening Identifies the Hsp70 Co-chaperone HDJ2 as a Hub for Anticancer Drug Resistance

Proteomic profiling of bladder cancer for precision medicine in the clinical setting: A review for the busy urologist

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