Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

Cruz, Isa N.; Coley, Helen M.; Kramer, Holger; Madhuri, Thumuluru Kavitha; Safuwan, Nur Arnida Mohammed; Angelino, Ana Rita; Yang, Min

doi:10.21873/cgp.20017

Cited by 56 publications

(53 citation statements)

References 48 publications

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“…Upon core biomarker filter analysis by IPA, two proteins, that is, AnxA6 and LDHA, found as potential biomarkers for OC. Downregulated expression of LDHA in OC, as found in our study, has also been reported previously . LDHA is responsible for enhanced glycolysis instead of oxidative phosphorylation in cancer cells for energy generation to satisfy the demands of rapidly multiplying cancer cells, the phenomenon called Warburg effect …”

Section: Discussionsupporting

confidence: 89%

“…Altered expression of annexins has earlier been reported in various human tumors contributing to cellular propagation, motility, cancer invasion, spread, angiogenesis, apoptosis, and drug resistance . The differential abundance of AnxA4 and AnxA5 in the present study showed consistency with the former OC proteomic data . Upregulated AnxA4 is described related to invasive progression and drug resistance in various cancers including OC .…”

Section: Discussionsupporting

confidence: 88%

“…Proteomics studies, involving in‐depth analysis of the tissue/plasma specimens, are expected to improve not only our understanding of mechanism of tumor development and/or progression but may also lead to development of novel therapeutic targets for disease cure. More specifically, identification of proteins differentially represented in OC tissues compared to normal ovarian tissues can provide potential diagnostic, prognostic, and therapeutic biomarkers and thus, may facilitate in deciding the available treatment choice(s) . Amongst the various proteomic approaches used for biomarker identification, 2D gel electrophoresis (2‐DE) followed by mass spectrometric (MS) identification of the differentially regulated molecules, has customarily been utilized in numerous malignancies …”

Section: Introductionmentioning

confidence: 99%

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Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

Noreen

Gardner

Fatima

et al. 2020

Proteomics Clinical Apps

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Purpose An early and accurate diagnosis of ovarian carcinoma (OC) may reduce morbidity and mortality of the patients. To improve the clinical outcome in OC patients, the present study is aimed at identifying robust biomarkers for early OC diagnosis. Experimental Design In order to look for early‐stage protein markers, a systematic protein profiling approach involving 2‐dimensional electrophoresis coupled with mass spectrometric analyses of human malignant and non‐malignant ovarian biopsy samples, is performed. Results Six 2D gel spots, corresponding to five proteins, display statistically significant differential expression in the tumor tissues compared to benign controls (FDR ≤ 0.05; PMF score ≥ 79). Ingenuity pathway analysis predicts two proteins, that is, Ca2+‐dependent membrane‐binding protein annexin A6 (AnxA6) and the metabolic enzyme l‐lactate dehydrogenase A chain, as potential predictive biomarkers. Increased expression of AnxA6 is further ascertained by Western blot and enzyme linked immunosorbent assay in the resected tissues and the plasma samples. The expression is found markedly increasing particularly in the advanced stage tumors. Conclusions and Clinical Relevance The significant upregulation of AnxA6 in OC, reported for the first time, is likely to provide insight into the mechanism of OC progression, which may lead to the design of potential diagnostic and therapeutic strategies.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

Noreen

Gardner

Fatima

et al. 2020

Proteomics Clinical Apps

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“…The Warburg effect has been hypothesised to be an adaptation mechanism in cancer cells to support the biosynthetic requirements of rapid proliferation. Alpha-enolase expression has been shown to be altered at the mRNA and/or protein level in a range of tumours [ Table 1], and generally upregulated in most, including acute myeloid leukaemia (AML), glioma, melanoma, lymphoma, and colorectal, endometrial, gastric, head and neck, liver, ovarian and pancreatic cancer [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] .…”

Section: Alpha-enolase Expression Is Altered In Tumours and Varies Wimentioning

confidence: 99%

“…Increased glycolysis is considered a hallmark of cancer [2] and investigating glycolytic enzymes may yield new therapeutic approaches for cancer treatment. Enolases are key glycolytic enzymes [3] , and increased expression of one isoform, a-enolase, has been identified in several cancer types [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] . This review provides an overview of the expression of a-enolase and key functions it controls in cancer cells, with a focus on the potential role of a-enolase as a cancer prognostic biomarker or therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

Unlikely role of glycolytic enzyme ��-enolase in cancer metastasis and its potential as a prognostic biomarker

Schofield¹,

Lincz²,

Skelding³

2020

JCMT

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Reliance on glycolysis for energy production is considered a hallmark of cancer and the glycolytic enzyme a-enolase is overexpressed in a range of cancer types. However, recent studies have revealed that a-enolase is involved in a variety of unrelated physiological processes and can be found in multiple unexpected cellular locations. This review focuses on the unlikely role of a-enolase as an extracellular plasminogen-binding receptor localised to the plasma membrane. Conversion of plasminogen to plasmin on the surface of cancer cells enhances their ability to invade through stroma by activating collagenases and degrading fibrin as well as extracellular matrix proteins. Increased expression of a-enolase is associated with increased migration and invasion of cancer cells, and decreased metastasis-free survival in patients with several cancer types, including non-small cell lung, pancreatic, breast and colorectal cancers. Due to its overexpression in a range of cancer types and multi-functional roles in key areas of tumour metabolism and metastasis, a-enolase may be useful as a universal cancer prognostic biomarker or therapeutic target.

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HSP90 identified by a proteomic approach as druggable target to reverse platinum resistance in ovarian cancer

et al. 2021

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Acquired resistance to platinum (Pt)‐based therapies is an urgent unmet need in the management of epithelial ovarian cancer (EOC) patients. Here, we characterized by an unbiased proteomics method three isogenic EOC models of acquired Pt resistance (TOV‐112D, OVSAHO, and MDAH‐2774). Using this approach, we identified several differentially expressed proteins in Pt‐resistant (Pt‐res) compared to parental cells and the chaperone HSP90 as a central hub of these protein networks. Accordingly, up‐regulation of HSP90 was observed in all Pt‐res cells and heat‐shock protein 90 alpha isoform knockout resensitizes Pt‐res cells to cisplatin (CDDP) treatment. Moreover, pharmacological HSP90 inhibition using two different inhibitors [17‐(allylamino)‐17‐demethoxygeldanamycin (17AAG) and ganetespib] synergizes with CDDP in killing Pt‐res cells in all tested models. Mechanistically, genetic or pharmacological HSP90 inhibition plus CDDP ‐induced apoptosis and increased DNA damage, particularly in Pt‐res cells. Importantly, the antitumor activities of HSP90 inhibitors (HSP90i) were confirmed both ex vivo in primary cultures derived from Pt‐res EOC patients ascites and in vivo in a xenograft model. Collectively, our data suggest an innovative antitumor strategy, based on Pt compounds plus HSP90i, to rechallenge Pt‐res EOC patients that might warrant further clinical evaluation.

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Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

Abstract: Abstract. Background: Carboplatin and paclitaxel

Cited by 56 publications

References 48 publications

Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

Unlikely role of glycolytic enzyme ��-enolase in cancer metastasis and its potential as a prognostic biomarker

HSP90 identified by a proteomic approach as druggable target to reverse platinum resistance in ovarian cancer

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