ECB-ART-49912
Cells
2019 Jul 31;88:. doi: 10.3390/cells8080806.
Show Gene links
Show Anatomy links
Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry.
Marrugal Á
,
Ferrer I
,
Pastor MD
,
Ojeda L
,
Quintanal-Villalonga Á
,
Carnero A
,
Molina-Pinelo S
,
Paz-Ares L
.
???displayArticle.abstract???
Heat shock protein 90 (HSP90) is an important chaperone in lung adenocarcinoma, with relevant protein drivers such as EGFR (epidermal growth factor receptor) and EML4-ALK (echinoderm microtubule-associated protein-like protein4 fused to anaplastic lymphoma kinase) depending on it for their correct function, therefore HSP90 inhibitors show promise as potential treatments for lung adenocarcinoma. To study responses to its inhibition, HSP90 was pharmacologically interrupted by geldanamycin and resorcinol derivatives or with combined inhibition of HSP90 plus HSP70 in lung adenocarcinoma cell lines. Two-dimensional electrophoresis was performed to identify proteomic profiles associated with inhibition which will help to understand the biological basis for the responses. HSP90 inhibition resulted in altered protein profiles that differed according the treatment condition studied. Results revealed 254 differentially expressed proteins after treatments, among which, eukaryotic translation initiation factor3 subunit I (eIF3i) and citrate synthase demonstrated their potential role as response biomarkers. The differentially expressed proteins also enabled signalling pathways involved in responses to be identified; these included apoptosis, serine-glycine biosynthesis and tricarboxylic acid cycle. The proteomic profiles identified here contribute to an improved understanding of HSP90 inhibition and open possibilities for the detection of potential response biomarkers which will be essential to maximize treatment efficacy in lung adenocarcinoma.
???displayArticle.pubmedLink??? 31370342
???displayArticle.pmcLink??? PMC6721529
???displayArticle.link??? Cells
???displayArticle.grants??? [+]
P30 CA008748 NCI NIH HHS
???attribute.lit??? ???displayArticles.show???
References [+] :
Ahlemann,
Carcinoma-associated eIF3i overexpression facilitates mTOR-dependent growth transformation.
2006, Pubmed
Ahlemann, Carcinoma-associated eIF3i overexpression facilitates mTOR-dependent growth transformation. 2006, Pubmed
Alves, Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma. 2018, Pubmed
Amelio, Serine and glycine metabolism in cancer. 2014, Pubmed
Anderson, The emerging role and targetability of the TCA cycle in cancer metabolism. 2018, Pubmed
Antonov, Bioinformatics analysis of the serine and glycine pathway in cancer cells. 2014, Pubmed
Ağababaoğlu, Chaperonin (HSP60) and annexin-2 are candidate biomarkers for non-small cell lung carcinoma. 2017, Pubmed
Bronner, Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. 1994, Pubmed
Bucci, Signal transduction gRABs attention. 2006, Pubmed
Butler, Maximizing the Therapeutic Potential of HSP90 Inhibitors. 2015, Pubmed
Cai, The predictive value of ERCC1 and p53 for the effect of panobinostat and cisplatin combination treatment in NSCLC. 2015, Pubmed
Chai, Heat shock protein 90 inhibitors augment endogenous wild-type p53 expression but down-regulate the adenovirally-induced expression by inhibiting a proteasome activity. 2018, Pubmed
Chan, Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. 2015, Pubmed
Chatterjee, HSP90 inhibitors in lung cancer: promise still unfulfilled. 2016, Pubmed
Chen, Targeting HSF1 sensitizes cancer cells to HSP90 inhibition. 2013, Pubmed
Chen, Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma. 2014, Pubmed
Cho, Application of proteomics in non-small-cell lung cancer. 2016, Pubmed
Choi, AUY922 effectively overcomes MET- and AXL-mediated resistance to EGFR-TKI in lung cancer cells. 2015, Pubmed
Chou, Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance. 2015, Pubmed
Conde, Modulation of Hsf1 activity by novobiocin and geldanamycin. 2009, Pubmed
Di Maro, Anterior gradient protein 2 promotes survival, migration and invasion of papillary thyroid carcinoma cells. 2014, Pubmed
Erlejman, Regulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression. 2014, Pubmed
Esfahani, HSP90 as a novel molecular target in non-small-cell lung cancer. 2016, Pubmed
Felip, Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non-Small Cell Lung Cancer. 2018, Pubmed
Gallegos Ruiz, Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target. 2008, Pubmed
Gao, Identification of DJ-1 as a contributor to multidrug resistance in human small-cell lung cancer using proteomic analysis. 2017, Pubmed
Garcia-Carbonero, Inhibition of HSP90 molecular chaperones: moving into the clinic. 2013, Pubmed
Giatromanolaki, Expression of enzymes related to glucose metabolism in non-small cell lung cancer and prognosis. 2017, Pubmed
Gomes-Duarte, eIF3: a factor for human health and disease. 2018, Pubmed
Grem, Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors. 2005, Pubmed
Grills, Gene expression meta-analysis identifies VDAC1 as a predictor of poor outcome in early stage non-small cell lung cancer. 2011, Pubmed
Hashimoto, Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer. 2019, Pubmed
Herbst, Lung cancer. 2008, Pubmed
Hershey, Regulation of protein synthesis and the role of eIF3 in cancer. 2010, Pubmed
Hershey, The role of eIF3 and its individual subunits in cancer. 2015, Pubmed
Hirakawa, The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells. 2015, Pubmed
Hu, Aberrant methylation of mutL homolog 1 is associated with increased risk of non-small cell lung cancer. 2018, Pubmed
Hua, Clinical significance of chromodomain helicase/ATPase DNA binding protein 1-like and human mutL homolog 1 gene expression in cholangiocarcinoma. 2018, Pubmed
Huang, Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. 2004, Pubmed
Jain, Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. 2012, Pubmed
Johnson, Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for EGFR-Mutant Lung Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. 2015, Pubmed
Joseph, Up-regulation of expression of translation factors--a novel molecular mechanism for cadmium carcinogenesis. 2004, Pubmed
Kang, The Haptoglobin β chain as a supportive biomarker for human lung cancers. 2011, Pubmed
Khalouei, Stress-induced localization of HSPA6 (HSP70B') and HSPA1A (HSP70-1) proteins to centrioles in human neuronal cells. 2014, Pubmed
Kim, Expression of anterior gradient 2 is decreased with the progression of human biliary tract cancer. 2014, Pubmed
Kobayashi, The anti-proliferative effect of heat shock protein 90 inhibitor, 17-DMAG, on non-small-cell lung cancers being resistant to EGFR tyrosine kinase inhibitor. 2012, Pubmed
Koizumi, Hsp90 inhibition overcomes HGF-triggering resistance to EGFR-TKIs in EGFR-mutant lung cancer by decreasing client protein expression and angiogenesis. 2012, Pubmed
Korfanty, Crosstalk between HSF1 and HSF2 during the heat shock response in mouse testes. 2014, Pubmed
Kriegs, Radiosensitization of NSCLC cells by EGFR inhibition is the result of an enhanced p53-dependent G1 arrest. 2015, Pubmed
Kudryavtsev, Induction of Hsp70 in tumor cells treated with inhibitors of the Hsp90 activity: A predictive marker and promising target for radiosensitization. 2017, Pubmed
Lai, p53 gene status modulates the chemosensitivity of non-small cell lung cancer cells. 2000, Pubmed
Lei, Antisense inhibition of translation initiation factor 3 reverses its oncogenic potential. 2002, Pubmed
Li, Review of aerobic glycolysis and its key enzymes - new targets for lung cancer therapy. 2015, Pubmed
Lin, Hsp90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53/ATM status in chronic lymphocytic leukaemia cells. 2008, Pubmed
Liu, Protein signature for non-small cell lung cancer prognosis. 2014, Pubmed
Lu, Comparative Proteomics of Chromium-Transformed Beas-2B Cells by 2D-DIGE and MALDI-TOF/TOF MS. 2018, Pubmed
Lu, Mortalin-p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy. 2011, Pubmed
Lu, MutL homolog 1 expression in thyroid carcinoma and its clinical significance. 2016, Pubmed
Maresh, Differential expression of anterior gradient gene AGR2 in prostate cancer. 2010, Pubmed
Marrugal, Proteomic-Based Approaches for the Study of Cytokines in Lung Cancer. 2016, Pubmed
Masuda, Rab37 is a novel mast cell specific GTPase localized to secretory granules. 2000, Pubmed
Matsuda, Molecular cloning and characterization of human MAWD, a novel protein containing WD-40 repeats frequently overexpressed in breast cancer. 2000, Pubmed
Mi, PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium. 2010, Pubmed
Millares, Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance. 2018, Pubmed
Na, Stress chaperone mortalin contributes to epithelial-mesenchymal transition and cancer metastasis. 2016, Pubmed
Nagano, Identification and evaluation of metastasis-related proteins, oxysterol binding protein-like 5 and calumenin, in lung tumors. 2015, Pubmed
Nakamura, HSP60 as a drug target. 2013, Pubmed
Nan, Early Candidate Biomarkers of Non-Small Cell Lung Cancer Are Screened and Identified in Premalignant Lung Lesions. 2017, Pubmed
Nathan, In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone. 1997, Pubmed
Neckers, Hsp90 molecular chaperone inhibitors: are we there yet? 2012, Pubmed
Nguyen, Identification of Novel Response and Predictive Biomarkers to Hsp90 Inhibitors Through Proteomic Profiling of Patient-derived Prostate Tumor Explants. 2018, Pubmed
Niu, [Effects of 17-AAG on the proliferation and apoptosis of human lung cancer A549 and H446 cells]. 2015, Pubmed
Normant, The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models. 2011, Pubmed , Echinobase
Okano, Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling. 2016, Pubmed
Pace, Hsp60, a novel target for antitumor therapy: structure-function features and prospective drugs design. 2013, Pubmed
Park, The HSP90 inhibitor, NVP-AUY922, sensitizes KRAS-mutant non-small cell lung cancer with intrinsic resistance to MEK inhibitor, trametinib. 2016, Pubmed
Pastor, Proteomic biomarkers in lung cancer. 2013, Pubmed
Pastor, Identification of proteomic signatures associated with lung cancer and COPD. 2013, Pubmed
Pavlova, The Emerging Hallmarks of Cancer Metabolism. 2016, Pubmed
Qi, EIF3i promotes colon oncogenesis by regulating COX-2 protein synthesis and β-catenin activation. 2014, Pubmed
Ramirez, Basal and stress-inducible expression of HSPA6 in human keratinocytes is regulated by negative and positive promoter regions. 2015, Pubmed
Riener, Loss of anterior gradient-2 expression is an independent prognostic factor in colorectal carcinomas. 2014, Pubmed
Rong, Molecular mechanism and targeted therapy of Hsp90 involved in lung cancer: New discoveries and developments (Review). 2018, Pubmed
Sequist, Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. 2010, Pubmed
Shi, Promoter methylation of human mutL homolog 1 and colorectal cancer risk: A meta-analysis. 2018, Pubmed
Shimamura, Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins. 2005, Pubmed
Shin, HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; Implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation. 2017, Pubmed
Siegel, Cancer statistics, 2018. 2018, Pubmed
Socinski, A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. 2013, Pubmed
Somasundaram, Personalized treatment of EGFR mutant and ALK-positive patients in NSCLC. 2014, Pubmed
Spilka, Eukaryotic translation initiation factors in cancer development and progression. 2013, Pubmed
Stanhill, Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells. 2006, Pubmed
Sun, Mortalin overexpression predicts poor prognosis in early stage of non-small cell lung cancer. 2017, Pubmed
Thomas, PANTHER: a library of protein families and subfamilies indexed by function. 2003, Pubmed
Thunnissen, Prognostic and predictive biomarkers in lung cancer. A review. 2014, Pubmed
Tsai, Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis. 2014, Pubmed
Tzeng, Phosphorylation of Rab37 by protein kinase C alpha inhibits the exocytosis function and metastasis suppression activity of Rab37. 2017, Pubmed
Ueno, Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer. 2012, Pubmed
Voruganti, Proteomic Profiling of Hsp90 Inhibitors. 2018, Pubmed
Walter, HSP90 promotes Burkitt lymphoma cell survival by maintaining tonic B-cell receptor signaling. 2017, Pubmed
Wang, Cancer cells harboring MET gene amplification activate alternative signaling pathways to escape MET inhibition but remain sensitive to Hsp90 inhibitors. 2009, Pubmed
Wang, Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma. 2013, Pubmed
Weidenauer, Proteomic interrogation of HSP90 and insights for medical research. 2017, Pubmed
Willis, Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis. 2016, Pubmed
Wu, Frequent down-regulation of hRAB37 in metastatic tumor by genetic and epigenetic mechanisms in lung cancer. 2009, Pubmed
Xu, Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition. 2007, Pubmed
Xu, Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma. 2011, Pubmed
Yuan, The translation initiation factor eIF3i up-regulates vascular endothelial growth factor A, accelerates cell proliferation, and promotes angiogenesis in embryonic development and tumorigenesis. 2014, Pubmed
Yun, Relevance of mortalin to cancer cell stemness and cancer therapy. 2017, Pubmed
Zerial, Rab proteins as membrane organizers. 2001, Pubmed
Zhang, eIF3i activity is critical for endothelial cells in tumor induced angiogenesis through regulating VEGFR and ERK translation. 2017, Pubmed
Zugazagoitia, Biological therapies in nonsmall cell lung cancer. 2017, Pubmed
Zweitzig, Physiological stress induces the metastasis marker AGR2 in breast cancer cells. 2007, Pubmed
da Rocha Dias, Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. 2005, Pubmed