Institute of Pharmacology

Konstantinidou Group

Group members

PD Dr. Georgia Konstantinidou, PhD

Group members

former Group members

Thomas Bertotto (2021)

Raphael Aregger MSc (2021)

Dr. Asmita Thapa postdoc (2021)

Thierry Paschoud MSc (2021)

Dr. Matteo Rossi Sebastiano PhD (2020); postdoc (2020)

Projects

Cancer cells undergo oncogene-directed reprogramming in order to meet the energetic and biosynthetic challenges of cell survival, growth and proliferation. Our lab aims at identifying vulnerabilities of cancer cells in order to reveal targets for the development of innovative therapeutic strategies. In particular, we focus on the signaling and lipid metabolic alterations in KRAS-induced lung and pancreatic cancer. We work on cell lines (using a combination of techniques in molecular biology, cell biology and biochemistry), mouse models of lung and pancreatic cancer and human specimens. Our Institute and our collaborator institutions provide state-of-the-art technologies which allow us to develop novel approaches to treat cancer.

Publications

BORIS

Jump to: 2023 | 2022 | 2021 | 2020 | 2019 | 2017 | 2016 | 2015 | 2013 | 2012 | 2010 | 2009 | 2008

2023

Deng, Haibin; Ge, Huixiang; Dubey, Christelle; Losmanova, Tereza; Medova, Michaela; Konstantinidou, Georgia; Mutlu, Seyran Mathilde; Birrer, Fabienne Esther; Brodie, Tess Melinda; Stroka, Deborah; Wang, Wenxiang; Peng, Ren-Wang; Dorn, Patrick; Marti, Thomas Michael (2023). An optimized protocol for the generation and monitoring of conditional orthotopic lung cancer in the KP mouse model using an adeno-associated virus vector compatible with biosafety level 1. Cancer immunology, immunotherapy : CII, 72(12), pp. 4457-4470. Springer 10.1007/s00262-023-03542-z

Saliakoura, Maria; Konstantinidou, Georgia (2023). Lipid Metabolic Alterations in KRAS Mutant Tumors: Unmasking New Vulnerabilities for Cancer Therapy. International journal of molecular sciences, 24(2) MDPI 10.3390/ijms24021793

2022

Saliakoura, Maria; Rossi Sebastiano, Matteo; Nikdima, Ioanna; Pozzato, Chiara; Konstantinidou, Georgia (2022). Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy. Journal of experimental & clinical cancer research, 41(1), p. 16. BioMed Central 10.1186/s13046-021-02231-y

2021

Yang, Zhang; Liang, Shun-Qing; Saliakoura, Maria; Yang, Haitang; Vassella, Erik; Konstantinidou, Georgia; Tschan, Mario; Hegedüs, Balazs; Zhao, Liang; Gao, Yanyun; Xu, Duo; Deng, Haibin; Marti, Thomas M; Kocher, Gregor J; Wang, Wenxiang; Schmid, Ralph A; Peng, Ren-Wang (2021). Synergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS-mutant cancer. EMBO molecular medicine, 13(9), e13193. EMBO Press 10.15252/emmm.202013193

Leroux, Cédric; Konstantinidou, Georgia (2021). Targeted Therapies for Pancreatic Cancer: Overview of Current Treatments and New Opportunities for Personalized Oncology. Cancers, 13(4) MDPI AG 10.3390/cancers13040799

2020

Saliakoura, Maria; Rossi Sebastiano, Matteo; Pozzato, Chiara; Heidel, Florian H.; Schnöder, Tina M.; Savic Prince, Spasenija; Bubendorf, Lukas; Pinton, Paolo; Schmid, Ralph A.; Baumgartner, Johanna; Freigang, Stefan; Berezowska, Sabina A.; Rimessi, Alessandro; Konstantinidou, Georgia (2020). PLCγ1 suppression promotes the adaptation of KRAS-mutant lung adenocarcinomas to hypoxia. Nature cell biology, 22(11), pp. 1382-1395. Springer Nature 10.1038/s41556-020-00592-8

Rossi Sebastiano, Matteo; Pozzato, Chiara; Saliakoura, Maria; Zhang, Yang; Peng, Ren-Wang; Galiè, Mirco; Oberson, Kevin; Simon, Hans-Uwe; Karamitopoulou, Evanthia; Konstantinidou, Georgia (2020). ACSL3-PAI-1 signaling axis mediates tumor-stroma cross-talk promoting pancreatic cancer progression. Science Advances, 6(44), pp. 1-15. American Association for the Advancement of Science 10.1126/sciadv.abb9200

Saliakoura, Maria; Reynoso-Moreno, Inés; Pozzato, Chiara; Rossi Sebastiano, Matteo; Galié, Mirco; Gertsch, Jürg; Konstantinidou, Georgia (2020). The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small cell lung cancer. Oncogene, 39(14), pp. 2948-2960. Springer Nature 10.1038/s41388-020-1196-5

Ramadori, Giorgio; Ioris, Rafael M; Villanyi, Zoltan; Firnkes, Raquel; Panasenko, Olesya O; Allen, George; Konstantinidou, Georgia; Aras, Ebru; Brenachot, Xavier; Biscotti, Tommasina; Charollais, Anne; Luchetti, Michele; Bezrukov, Fedor; Santinelli, Alfredo; Samad, Muntaha; Baldi, Pierre; Collart, Martine A; Coppari, Roberto (2020). FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth. Cell reports, 30(11), pp. 3851-863. Cell Press 10.1016/j.celrep.2020.02.082

Konstantinidou, Georgia; Rimessi, Alessandro (2020). Editorial: Oncogenic RAS-Dependent Reprogramming of Cellular Plasticity. Frontiers in oncology, 10(588), p. 588. Frontiers Research Foundation 10.3389/fonc.2020.00588

2019

Rossi Sebastiano, Matteo; Konstantinidou, Georgia (2019). Targeting Long Chain Acyl-CoA Synthetases for Cancer Therapy. International journal of molecular sciences, 20(15) MDPI 10.3390/ijms20153624

2017

Ioris, Rafael M.; Galié, Mirco; Ramadori, Giorgio; Anderson, Jason G.; Charollais, Anne; Konstantinidou, Georgia; Brenachot, Xavier; Aras, Ebru; Goga, Algera; Ceglia, Nicholas; Sebastián, Carlos; Martinvalet, Denis; Mostoslavsky, Raul; Baldi, Pierre; Coppari, Roberto (2017). SIRT6 Suppresses Cancer Stem-like Capacity in Tumors with PI3K Activation Independently of Its Deacetylase Activity. Cell reports, 18(8), pp. 1858-1868. Cell Press 10.1016/j.celrep.2017.01.065

2016

Padanad, Mahesh S; Konstantinidou, Georgia; Venkateswaran, Niranjan; Melegari, Margherita; Rindhe, Smita; Mitsche, Matthew; Yang, Chendong; Batten, Kimberly; Huffman, Kenneth E; Liu, Jingwen; Tang, Ximing; Rodriguez-Canales, Jaime; Kalhor, Neda; Shay, Jerry W; Minna, John D; McDonald, Jeffrey; Wistuba, Ignacio I; DeBerardinis, Ralph J; Scaglioni, Pier Paolo (2016). Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis. Cell reports, 16(6), pp. 1614-1628. Cell Press 10.1016/j.celrep.2016.07.009

2015

Ramadori, Giorgio; Konstantinidou, Georgia; Venkateswaran, Niranjan; Biscotti, Tommasina; Morlock, Lorraine; Galié, Mirco; Williams, Noelle S.; Luchetti, Michele; Santinelli, Alfredo; Scaglioni, Pier Paolo; Coppari, Roberto (2015). Diet-Induced Unresolved ER Stress Hinders KRAS-Driven Lung Tumorigenesis. Cell metabolism, 21(1), pp. 117-125. Cell Press 10.1016/j.cmet.2014.11.020

Gaubitz, Christl; Oliveira, Taiana M.; Prouteau, Manoel; Leitner, Alexander; Karuppasamy, Manikandan; Konstantinidou, Georgia; Rispal, Delphine; Eltschinger, Sandra; Robinson, Graham C.; Thore, Stéphane; Aebersold, Ruedi; Schaffitzel, Christiane; Loewith, Robbie (2015). Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2. Molecular cell, 58(6), pp. 977-988. Cell Press 10.1016/j.molcel.2015.04.031

2013

Konstantinidou, Georgia; Ramadori, Giorgio; Torti, Francesca; Kangasniemi, Kim; Ramirez, Rachel E.; Cai, Yiran; Behrens, Carmen; Dellinger, Michael T.; Brekken, Rolf A.; Wistuba, Ignacio I.; Heguy, Adriana; Teruya-Feldstein, Julie; Scaglioni, Pier Paolo (2013). RHOA-FAK Is a Required Signaling Axis for the Maintenance of KRAS-Driven Lung Adenocarcinomas. Cancer discovery, 3(4), pp. 444-457. American Association for Cancer Research 10.1158/2159-8290.CD-12-0388

2012

Rabellino, A.; Carter, B.; Konstantinidou, Georgia; Wu, S.-Y.; Rimessi, A.; Byers, L. A.; Heymach, J. V.; Girard, L.; Chiang, C.-M.; Teruya-Feldstein, J.; Scaglioni, P. P. (2012). The SUMO E3-ligase PIAS1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA. Cancer research, 72(9), pp. 2275-2284. American Association for Cancer Research AACR 10.1158/0008-5472.CAN-11-3159

Scaglioni, Pier Paolo; Rabellino, Andrea; Yung, Thomas M.; Bernardi, Rosa; Choi, Sooyeon; Konstantinidou, Georgia; Nardella, Caterina; Cheng, Ke; Pandolfi, Pier Paolo (2012). Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K-RAS-induced cellular senescence. EMBO molecular medicine, 4(7), pp. 594-602. EMBO Press 10.1002/emmm.201200233

Bisaro, Brigitte; Montani, Maura; Konstantinidou, Georgia; Marchini, Cristina; Pietrella, Lucia; Iezzi, Manuela; Galiè, Mirco; Orso, Francesca; Camporeale, Annalisa; Colombo, Shana M; Di Stefano, Paola; Tornillo, Giusy; Camacho-Leal, Maria P; Turco, Emilia; Taverna, Daniela; Cabodi, Sara; Amici, Augusto; Defilippi, Paola (2012). p130Cas/Cyclooxygenase-2 axis in the control of mesenchymal plasticity of breast cancer cells. Breast cancer research, 14(5), R137. BioMed Central Ltd. 10.1186/bcr3342

2010

Marchini, Cristina; Montani, Maura; Konstantinidou, Georgia; Orrù, Rita; Mannucci, Silvia; Ramadori, Giorgio; Gabrielli, Federico; Baruzzi, Anna; Berton, Giorgio; Merigo, Flavia; Fin, Stefania; Iezzi, Manuela; Bisaro, Brigitte; Sbarbati, Andrea; Zerani, Massimo; Galiè, Mirco; Amici, Augusto; Shioda, Toshi (2010). Mesenchymal/Stromal Gene Expression Signature Relates to Basal-Like Breast Cancers, Identifies Bone Metastasis and Predicts Resistance to Therapies. PLoS ONE, 5(11), e14131. Public Library of Science 10.1371/journal.pone.0014131

2009

Konstantinidou, Georgia; Bey, E. A.; Rabellino, A.; Schuster, K.; Maira, M. S.; Gazdar, A. F.; Amici, A.; Boothman, D. A.; Scaglioni, P. P. (2009). Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Blockade Is an Effective Radiosensitizing Strategy for the Treatment of Non-Small Cell Lung Cancer Harboring K-RAS Mutations. Cancer research, 69(19), pp. 7644-7652. American Association for Cancer Research AACR 10.1158/0008-5472.CAN-09-0823

2008

Scaglioni, P. P.; Yung, T. M.; Choi, S. C.; Baldini, C.; Konstantinidou, Georgia; Pandolfi, P. P. (2008). CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor. Molecular and cellular biochemistry, 316(1-2), pp. 149-154. Springer 10.1007/s11010-008-9812-7

Galiè, M; Konstantinidou, Georgia; Peroni, D; Scambi, I; Marchini, C; Lisi, V; Krampera, M; Magnani, P; Merigo, F; Montani, M; Boschi, F; Marzola, P; Orrù, R; Farace, P; Sbarbati, A; Amici, A (2008). Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice. Oncogene, 27(18), pp. 2542-2551. Nature Publishing Group 10.1038/sj.onc.1210920

Selected Publications:

Ioris R.M., Galié M.1, Ramadori G., Anderson J.G., Charollais A., Konstantinidou G., Brenachot X., Aras E., Goga A., Ceglia N., Sebastián C., Martinvalet D., Mostoslavsky R., Baldi P., Coppari R. SIRT6 suppresses cancer stem-like capacity in tumors with PI3K activation independently of its deacetylase activity. Cell Reports 2017 DOI: 10.1016/j.celrep.2017.01.065

Mahesh S. Padanad#, Georgia Konstantinidou#, Niranjan Venkateswaran, Margherita Melegari, Smita Rindhe, Matthew Mitsche, Chendong Yang, Kimberly Batten, Kenneth E. Huffman, Jingwen Liu, Ximing Tang, Jaime Rodriguez-Canales, Neda Kalhor, Jerry W. Shay, John D. Minna, Jeffrey McDonald, Ignacio I. Wistuba, Ralph J. DeBerardinis, and Pier Paolo Scaglioni. Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis. Cell Reports 2016 DOI: 10.1016/j.celrep.2016.07.009

# Equal contribution.

Christl Gaubitz, Taiana M. Oliveira, Manoel Prouteau, Alexander Leitner, Manikandan Karuppasamy, Georgia Konstantinidou, Delphine Rispal, Sandra Eltschinger, Graham C. Robinson, Stéphane Thore, Ruedi Aebersold, Robbie Loewith, and Christiane Schaffitzel. Structural basis of the rapamycin insensitivity of Target Of Rapamycin Complex 2. Mol. Cell 2015 DOI: 10.1016/j.molcel.2015.04.031

Giorgio Ramadori#, Georgia Konstantinidou#, Niranjan Venkateswaran, Tommasina Biscotti, Lorraine Morlock, Mirco Galie´, Noelle S. Williams, Michele Luchetti, Alfredo Santinelli, Pier Paolo Scaglioni and Roberto Coppari. Diet-induced Unresolved ER stress Hinders KRAS-Driven Lung Tumorigenesis. Cell Metab. 2014 DOI: 10.1016/j.cmet.2014.11.020

# Equal contribution.

Konstantinidou G, Ramadori G, Torti F, Kangasniemi K, Ramirez RE, Cai Y, Behrens C, Dellinger MT, Brekken RA, Wistuba II, Heguy A, Teruya-Feldstein J, Scaglioni PP. RHOA-FAK is a required signaling axis for the maintenance of KRAS-driven lung adenocarcinomas. Cancer Discov. 2013 DOI: 10.1158/2159-8290.CD-12-0388

Konstantinidou G, Bey EA, Rabellino A, Schuster K, Maira MS, Gazdar AF, Amici A, Boothman DA, Pier Paolo Scaglioni. Dual PI3K/mTOR blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS Mutations. Cancer Res 2009. DOI: 10.1158/0008-5472.CAN-09-0823