Imperial College London

Dr Olivier E. Pardo

Faculty of MedicineDepartment of Surgery & Cancer

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2814o.pardo Website CV

 
 
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Location

 

131ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

50 results found

Poursaitidis I, Wang X, Crighton T, Labuschagne C, Mason D, Cramer SL, Triplett K, Roy R, Pardo OE, Seckl MJ, Rowlinson SW, Stone E, Lamb RFet al., 2017, Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine, CELL REPORTS, Vol: 18, Pages: 2547-2556, ISSN: 2211-1247

JOURNAL ARTICLE

Li H, Stokes W, Chater E, Roy R, de Bruin E, Hu Y, Liu Z, Smit EF, Heynen GJ, Downward J, Seckl MJ, Wang Y, Tang H, Pardo OEet al., 2016, Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer., Cell Discov, Vol: 2, ISSN: 2056-5968

Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through the secondary T790M EGFR mutation. To overcome this problem, we analysed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M EGFR cells. We also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. Decreased transcription of the GSH-synthesising enzymes (GCLC and GSS) due to the inhibition of NRF2 was responsible for low GSH levels in resistant cells that was directly linked to the T790M mutation. T790M EGFR clinical samples also showed decreased expression of these key enzymes; increasing intra-tumoural GSH levels with a small-molecule GST inhibitor re-sensitised resistant tumours to erlotinib in mice. Thus, we identified a new resistance pathway controlled by EGFR T790M and a therapeutic strategy to tackle this problem in the clinic.

JOURNAL ARTICLE

Pardo OE, Castellano L, Munro CE, Hu Y, Mauri F, Krell J, Lara R, Pinho FG, Choudhury T, Frampton AE, Pellegrino L, Pshezhetskiy D, Wang Y, Waxman J, Seckl MJ, Stebbing Jet al., 2016, miR-515-5p controls cancer cell migration through MARK4 regulation, EMBO REPORTS, Vol: 17, Pages: 570-584, ISSN: 1469-221X

JOURNAL ARTICLE

Pardo OE, 2015, Meningioma dissemination and growth: a role for microRNAs, ONCOGENE, Vol: 34, Pages: 1743-1744, ISSN: 0950-9232

JOURNAL ARTICLE

Schlegel CR, Georgiou ML, Misterek MB, Stoecker S, Chater ER, Munro CE, Pardo OE, Seckl MJ, Costa-Pereira APet al., 2015, DAPK2 regulates oxidative stress in cancer cells by preserving mitochondrial function, CELL DEATH & DISEASE, Vol: 6, ISSN: 2041-4889

JOURNAL ARTICLE

Hoeland K, Boller D, Hagel C, Dolski S, Treszl A, Pardo OE, Cwiek P, Salm F, Leni Z, Shepherd PR, Styp-Rekowska B, Djonov V, von Bueren AO, Frei K, Arcaro Aet al., 2014, Targeting Class I-A PI3K Isoforms Selectively Impairs Cell Growth, Survival, and Migration in Glioblastoma, PLOS ONE, Vol: 9, ISSN: 1932-6203

JOURNAL ARTICLE

Roy R, Durie D, Li H, Liu B-Q, Skehel JM, Mauri F, Cuorvo LV, Barbareschi M, Guo L, Holcik M, Seckl MJ, Pardo OEet al., 2014, hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling, NUCLEIC ACIDS RESEARCH, Vol: 42, Pages: 12483-12497, ISSN: 0305-1048

JOURNAL ARTICLE

Vincent EE, Elder DJE, O'Flaherty L, Pardo OE, Dzien P, Phillips L, Morgan C, Pawade J, May MT, Sohail M, Hetzel MR, Seckl MJ, Tavaré JMet al., 2014, Glycogen synthase kinase 3 protein kinase activity is frequently elevated in human non-small cell lung carcinoma and supports tumour cell proliferation., PLoS One, Vol: 9

BACKGROUND: Glycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including in non-small cell lung carcinoma (NSCLC). We examined the undefined role of GSK3 protein kinase activity in tissue from human NSCLC. METHODS: The expression and protein kinase activity of GSK3 was determined in 29 fresh frozen samples of human NSCLC and patient-matched normal lung tissue by quantitative immunoassay and western blotting for the phosphorylation of three distinct GSK3 substrates in situ (glycogen synthase, RelA and CRMP-2). The proliferation and sensitivity to the small-molecule GSK3 inhibitor; CHIR99021, of NSCLC cell lines (Hcc193, H1975, PC9 and A549) and non-neoplastic type II pneumocytes was further assessed in adherent culture. RESULTS: Expression and protein kinase activity of GSK3 was elevated in 41% of human NSCLC samples when compared to patient-matched control tissue. Phosphorylation of GSK3α/β at the inhibitory S21/9 residue was a poor biomarker for activity in tumour samples. The GSK3 inhibitor, CHIR99021 dose-dependently reduced the proliferation of three NSCLC cell lines yet was ineffective against type II pneumocytes. CONCLUSION: NSCLC tumours with elevated GSK3 protein kinase activity may have evolved dependence on the kinase for sustained growth. Our results provide further important rationale for exploring the use of GSK3 inhibitors in treating NSCLC.

JOURNAL ARTICLE

Kaliszczak M, Pardo OE, Seckl MJ, Aboagye EOet al., 2013, HDAC6 inhibitor C1A abrogates the recruitment of the autophagic machinery and synergizes with proteasome, src kinase, and PI3K-mTOR inhibition., MOLECULAR CANCER THERAPEUTICS, Vol: 12, ISSN: 1535-7163

JOURNAL ARTICLE

Lara R, Seckl MJ, Pardo OE, 2013, The p90 RSK Family Members: Common Functions and Isoform Specificity, CANCER RESEARCH, Vol: 73, Pages: 5301-5308, ISSN: 0008-5472

JOURNAL ARTICLE

Pardo OE, Seckl MJ, 2013, S6K2: The Neglected S6 Kinase Family Member., Front Oncol, Vol: 3, ISSN: 2234-943X

S6 kinase 2 (S6K2) is a member of the AGC kinases super-family. Its closest homolog, S6K1, has been extensively studied along the years. However, due to the belief in the community that the high degree of identity between these two isoforms would translate in essentially identical biological functions, S6K2 has been largely neglected. Nevertheless, recent research has clearly highlighted that these two proteins significantly differ in their roles in vitro as well as in vivo. These findings are significant to our understanding of S6 kinase signaling and the development of therapeutic strategies for several diseases including cancer. Here, we will focus on S6K2 and review the protein-protein interactions and specific substrates that determine the selective functions of this kinase.

JOURNAL ARTICLE

Seckl MJ, Roy R, Mauri F, Hue L, Jordan L, Skehel M, Lin G, Holcik M, Pardo Oet al., 2013, FGF-2 INDUCES CHEMORESISTANCE IN MODEL AND LUNG CANCER CELLS THROUGH S6K2/HNRNPA1-MEDIATED ENHANCED TRANSLATION OF ANTI-APOPTOTIC PROTEINS, JOURNAL OF THORACIC ONCOLOGY, Vol: 8, Pages: S1037-S1038, ISSN: 1556-0864

JOURNAL ARTICLE

Liwak U, Thakor N, Jordan LE, Roy R, Lewis SM, Pardo OE, Seckl M, Holcik Met al., 2012, Tumor Suppressor PDCD4 Represses Internal Ribosome Entry Site-Mediated Translation of Antiapoptotic Proteins and Is Regulated by S6 Kinase 2, MOLECULAR AND CELLULAR BIOLOGY, Vol: 32, Pages: 1818-1829, ISSN: 0270-7306

JOURNAL ARTICLE

De Laurentiis A, Pardo OE, Palamidessi A, Jackson SP, Schoenwaelder SM, Reichmann E, Scita G, Arcaro Aet al., 2011, The catalytic class I-A PI3K isoforms play divergent roles in breast cancer cell migration, CELLULAR SIGNALLING, Vol: 23, Pages: 529-541, ISSN: 0898-6568

JOURNAL ARTICLE

Lara R, Mauri F, Taylor H, Derua R, Shia A, Gray C, Nicols A, Shiner RJ, Schofield EE, Bates P, Waelkens E, Dallman M, Lamb J, Zicha D, Downward J, Seckl M, Pardo Oet al., 2011, IDENTIFICATION OF RSK1 AS A KEY MODULATOR OF LUNG CANCER METASTASIS, JOURNAL OF THORACIC ONCOLOGY, Vol: 6, Pages: S514-S515, ISSN: 1556-0864

JOURNAL ARTICLE

Lara R, Mauri FA, Taylor H, Derua R, Shia A, Gray C, Nicols A, Shiner RJ, Schofield E, Bates PA, Waelkens E, Dallman M, Lamb J, Zicha D, Downward J, Seckl MJ, Pardo OEet al., 2011, An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis, ONCOGENE, Vol: 30, Pages: 3513-3521, ISSN: 0950-9232

JOURNAL ARTICLE

Lara R, Mauri FA, Taylor H, Derua R, Shia A, Gray C, Nicols A, Shiner RJ, Schofield E, Bates PA, Waelkens E, Dallman M, Lamb J, Zicha D, Downward J, Seckl MJ, Pardo OEet al., 2011, An siRNA screen identifies Rsk1 as a key modulator of lung cancer metastasis, CANCER RESEARCH, Vol: 71, ISSN: 0008-5472

JOURNAL ARTICLE

Rupniewska E, Mauri F, Watling D, Pardo O, Seckl Met al., 2011, ROLE OF SRC FAMILY KINASES IN NSCLC: AUTOPHAGY INHIBITORS POTENTIATE KILLING EFFECTS OF DASATINIB, JOURNAL OF THORACIC ONCOLOGY, Vol: 6, Pages: S744-S745, ISSN: 1556-0864

JOURNAL ARTICLE

Goh ETH, Pardo OE, Michael N, Niewiarowski A, Totty N, Volkova D, Tsaneva IR, Seckl MJ, Gout Iet al., 2010, Involvement of Heterogeneous Ribonucleoprotein F in the Regulation of Cell Proliferation via the Mammalian Target of Rapamycin/S6 Kinase 2 Pathway, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 285, Pages: 17065-17076, ISSN: 0021-9258

JOURNAL ARTICLE

Rupniewska E, Watling D, Mauri FA, Pardo OE, Seckl MJet al., 2010, Src family kinases in lung cancer, 21st Meeting of the European-Association-for-Cancer-Research, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 95-95, ISSN: 1359-6349

CONFERENCE PAPER

Lara R, Mauri F, Gray C, Nicols A, Schofield E, Bates P, Zicha D, Downward J, Seckl M, Pardo Oet al., 2009, An siRNA screen identifies RSK family members as key regulator of lung cancer metastasis, CANCER RESEARCH, Vol: 69, ISSN: 0008-5472

JOURNAL ARTICLE

Marinov M, Ziogas A, Pardo OE, Tan LT, Dhillon T, Mauri FA, Lane HA, Lemoine NR, Zangemeister-Wittke U, Seckl MJ, Arcaro Aet al., 2009, AKT/mTOR Pathway Activation and BCL-2 Family Proteins Modulate the Sensitivity of Human Small Cell Lung Cancer Cells to RAD001, CLINICAL CANCER RESEARCH, Vol: 15, Pages: 1277-1287, ISSN: 1078-0432

JOURNAL ARTICLE

Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B, Lemoine NR, Stamp GW, Aboagye EO, Seckl MJet al., 2009, The Fibroblast Growth Factor Receptor Inhibitor PD173074 Blocks Small Cell Lung Cancer Growth In vitro and In vivo, CANCER RESEARCH, Vol: 69, Pages: 8645-8651, ISSN: 0008-5472

JOURNAL ARTICLE

Seckl M, Pardo OE, Lara R, Mauri F, Bates P, Zicha D, Downward Jet al., 2009, RNAi library screen reveals RSK1 as a key regulator of lung cancer metastasis, JOURNAL OF THORACIC ONCOLOGY, Vol: 4, Pages: S559-S560, ISSN: 1556-0864

JOURNAL ARTICLE

Seckl MJ, Pardo OE, Aboagye EO, Latigo J, Stamp G, Lemoine N, Spencer-Dean Bet al., 2009, The FGF receptor (FGFR) inhibitor PD0173074 blocks SCLC growth in vitro and in vivo, JOURNAL OF THORACIC ONCOLOGY, Vol: 4, Pages: S385-S385, ISSN: 1556-0864

JOURNAL ARTICLE

Pardo O, Downward J, Seckl MJ, 2008, Protein Complex involving PKCepsilon, BRaf and S6K2 and uses, WO 2008/078057 A1

PATENT

Yuan M, Tomlinson V, Lara R, Holliday D, Chelala C, Harada T, Gangeswaran R, Manson-Bishop C, Smith P, Danovi SA, Pardo O, Crook T, Mein CA, Lemoine NR, Jones LJ, Basu Set al., 2008, Yes-associated protein (YAP) functions as a tumor suppressor in breast, CELL DEATH AND DIFFERENTIATION, Vol: 15, Pages: 1752-1759, ISSN: 1350-9047

JOURNAL ARTICLE

Charles Swanton, Michela Marani, Olivier Pardo, Patricia H Warne, Gavin Kelly, Erik Sahai, Frederic Elustondo, Jenny Chang, Jillian Temple, Ahmed A Ahmed, James D Brenton, Julian Downward, Barbara Nickeet al., 2007, Regulators of Mitotic Arrest and Ceramide Metabolism Are Determinants of Sensitivity to Paclitaxel and Other Chemotherapeutic Drugs, Cancer Cell, Vol: 11, Pages: 498-512

JOURNAL ARTICLE

Marinov M, Ziogas A, Pardo OE, Tan LT, Lane HA, Lemoine NR, Zangemeister-Wittke U, Seckl MJ, Arcaro Aet al., 2007, Akt/mTOR pathway activation and Bcl-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001 (Everolimus), MOLECULAR CANCER THERAPEUTICS, Vol: 6, Pages: 3409S-3409S, ISSN: 1535-7163

JOURNAL ARTICLE

Katso RM, Pardo OE, Palamidessi A, Franz CM, Marinov M, De Laurentiis A, Downward J, Scita G, Ridley AJ, Waterfield MD, Arcaro Aet al., 2006, Phosphoinositide 3-Kinase C2beta regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms., Mol Biol Cell, Vol: 17, Pages: 3729-3744, ISSN: 1059-1524

Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein-protein and protein-lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2beta (PI3KC2beta) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb2. Increased expression of PI3KC2beta stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2beta reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2beta-overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms.

JOURNAL ARTICLE

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