Molecular carcinogenesis studies aim to dissect the molecular aspects of cancer initiation and progression and use this information to develop more effective treatments and prevention strategies. Today, molecular mechanisms associated with different cancers are partly being deciphered by functional genomics strategies, leading to translational research-supported novel discoveries of potential therapeutic stratifications designed to counteract or actually reverse such mechanisms. As a molecular carcinogenesis and functional genomics laboratory, we adapt traditional molecular cancer biology and classical biochemical approaches to next generation technologies (e.g. genome engineering and high-throughput functional screening platforms) and aim to implement an ideal research environment for identification and development of targeted cancer therapies. Our ambition is to advance knowledge on carcinogenesis mechanisms and explore drug targets for cancer.
Overall goal is to pursue a research program that utilizes functional genomics approaches and state-of-the-art tools for the understanding and the unraveling of cellular and molecular underpinnings of carcinogenesis and develops effective strategies for the discovery of cancer vulnerabilities, and hence potential future cancer drug targets. In this context, we are interested in the following research themes: (i) understanding why and how non-small cell lung cancer (NSCLC) cells become resistant to targeted therapies, (ii) mapping out cancer cell essential genes and dependencies across cancer types using functional genomics screens, (iii) understanding and mining of the molecular mechanisms of cancer cell senescence and identifying novel druggable cellular targets in senescence-resistance.
In order to do so, our lab is adopting the most comprehensive tools and relevant models for the examination of biological pathways and disease pathobiology.
We undertake a wide range of research efforts focused on the following major areas of investigation: (1) identification and characterization of the mechanisms driving cancer; (2) druggable target identification and validation against such mechanisms. The close proximity to basic and translational research for interdisciplinary collaboration is invaluable in the selection and validation of novel cancer drug discovery targets. Our lab is at the center of characterization of cancer-specific vulnerabilities using high-throughput data combined with information on genomic abnormalities in order to increase research opportunities and support improved treatment of such diseases.
Medine Zeynep Gungor, Merve Uysal, Serif Senturk. The Bright and the Dark Side of TGF-β Signaling in Hepatocellular Carcinoma: Mechanisms, Dysregulation, and Therapeutic Implications. Cancers. 2022 February ; 14 (4) : 940. doi:10.3390/cancers14040940. Download
Yagmur Toktay, Bengisu Dayanc, Serif Senturk. Engineering and Validation of a Dual Luciferase Reporter System for Quantitative and Systematic Assessment of Regulatory Sequences in Chinese Hamster Ovary Cells. Scientific Reports. 2022 April ; 12 . doi:10.1038/s41598-022-09887-2. Download
Dilara Demirci, Bengisu Dayanc, Fatma Aybuke Mazi, Serif Senturk. The Jekyll and Hyde of Cellular Senescence in Cancer. Cells. 2021 January ; 10 (2) : 208. doi:10.3390/cells10020208. Download
Daniel J. Klionsky and Co-authors. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 February ; 17 (1) : 1-382. doi:10.1080/15548627.2020.1797280. Download
Hasan Akbaba, Gülşah Erel-Akbaba, Serif Senturk. Recruitment of solid lipid nanoparticles for the delivery of CRISPR/Cas9: primary evaluation of anticancer gene editing. Nanomedicine. 2021 May ; 16 (12) : 963–978. doi:10.2217/nnm-2020-0412. Download
Polona Safaric Tepes, Debjani Pal, Trine Lindsted, Ingrid Ibarra, Amaja Lujambio, Vilma Jimenez Sabinina, Serif Senturk, Madison Miller, Navya Korimerla, Jiahao Huang, Larry Glassman, Paul Lee, David Zeltsman, Kevin Hyman, Michael Esposito, Gregory J. Hannon, Raffaella Sordella. An epigenetic switch regulates the ontogeny of AXL-positive/EGFR-TKI resistant cells by modulating miR-335 expression. eLife. 2021 July . doi:10.7554/eLife.66109. Download
Karabicici M, Azbazdar Y, Ozhan G, Senturk S, Firtina Karagonlar Z, Erdal E. Changes in Wnt and TGF-β Signaling Mediate the Development of Regorafenib Resistance in Hepatocellular Carcinoma Cell Line HuH7.. Frontiers in cell and developmental biology. 2021 August ; 9 : 639779. doi:10.3389/fcell.2021.639779. Download
Zeynep Güngör, Merve Uysal, Mehmet Öztürk, Şerif Şentürk. Systematic Analysis of Cytostatic TGF-Beta Response in Mesenchymal-Like Hepatocellular Carcinoma Cell Lines. Journal of Gastrointestinal Cancer. 2021 August . doi:10.1007/s12029-021-00704-z. Download
Tugce Batur, Ayse Argundogan, Umur Keles, Zeynep Mutlu, Hani Alotaibi, Serif Senturk, Mehmet Ozturk. AXL knock-out in SNU475 hepatocellular carcinoma cells provides evidence for lethal effect associated with G2 arrest and polyploidization. International Journal of Molecular Sciences. 2021 December ; 22 (24) : 13247. doi:10.3390/ijms222413247. Download
Ece Cakiroglu, Serif Senturk. Genomics and Functional Genomics of Malignant Pleural Mesothelioma. International Journal of Molecular Sciences. 2020 September ; 21 (17) : E6342. doi:10.3390/ijms21176342. Download
Ozgun G, Senturk S, Erkek-Ozhan S. Retinoic acid signaling and bladder cancer: Epigenetic deregulation, therapy and beyond.. International journal of cancer. 2020 October . doi:10.1002/ijc.33374. Download
Soheil Akbari, Nur Arslan, Şerif Şentürk, Esra Erdal. Next-Generation Liver Medicine Using Organoid Models. Frontiers in Cell and Developmental Biology-Stem Cell Research. 2019 December ; 7 : 345. doi:10.3389/fcell.2019.00345. Download
Aysim Gunes, Ezgi Bagirsakci, Evin Iscan, Gulcin Cakan-Akdogan, Umut Aykutlu, Serif Senturk, Gunes Ozhan, Esra Erdal, Deniz Nart, Funda Yilmaz Barbet, Nese Atabey. Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma. Oncotarget. 2018 ; 9 (96) : 36849-36866. doi:10.18632/oncotarget.26402. Download
Senturk S, Shirole NH, Nowak DG, Corbo V, Pal D, Vaughan A, Tuveson DA, Trotman LC, Kinney JB, Sordella R. Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization. Nature communications. 2017 February ; 8 : 14370. doi:10.1038/ncomms14370. Download
Shirole NH, Pal D, Kastenhuber ER, Senturk S, Boroda J, Pisterzi P, Miller M, Munoz G, Anderluh M, Ladanyi M, Lowe SW, Sordella R. Correction: TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. eLife. 2017 February ; 6 . doi:10.7554/eLife.25532. Download
Shirole NH, Pal D, Kastenhuber ER, Senturk S, Boroda J, Pisterzi P, Miller M, Munoz G, Anderluh M, Ladanyi M, Lowe SW, Sordella R. TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. eLife. 2016 October ; 5 : e17929. doi:10.7554/eLife.25532. Download
Shirole NH, Pal D, Kastenhuber ER, Senturk S, Boroda J, Pisterzi P, Miller M, Munoz G, Anderluh M, Ladanyi M, Lowe SW, Sordella R. TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. eLife. 2016 October ; 5 . doi:10.7554/eLife.17929. Download
Nowak DG, Cho H, Herzka T, Watrud K, DeMarco DV, Wang VM, Senturk S, Fellmann C, Ding D, Beinortas T, Kleinman D, Chen M, Sordella R, Wilkinson JE, Castillo-Martin M, Cordon-Cardo C, Robinson BD, Trotman LC. MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2.. Cancer discovery. 2015 June ; 5 (6) : 636-51. doi:10.1158/2159-8290.CD-14-1113. Download
Senturk S, Yao Z, Camiolo M, Stiles B, Rathod T, Walsh AM, Nemajerova A, Lazzara MJ, Altorki NK, Krainer A, Moll UM, Lowe SW, Cartegni L, Sordella R. p53Ψ is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state.. Proceedings of the National Academy of Sciences of the United States of America. 2014 August ; 111 (32) : E3287-96. doi:10.1073/pnas.1321640111. Download
Mender I, Senturk S, Ozgunes N, Akcali KC, Kletsas D, Gryaznov S, Can A, Shay JW, Dikmen ZG. Imetelstat (a telomerase antagonist) exerts off‑target effects on the cytoskeleton.. International journal of oncology. 2013 May ; 42 (5) : 1709-15. doi:10.3892/ijo.2013.1865. Download
Sucularli C, Senturk S, Ozturk M, Konu O. Dose- and time-dependent expression patterns of zebrafish orthologs of selected E2F target genes in response to serum starvation/replenishment.. Molecular biology reports. 2011 August ; 38 (6) : 4111-23. doi:10.1007/s11033-010-0531-2. Download
Buontempo F, Ersahin T, Missiroli S, Senturk S, Etro D, Ozturk M, Capitani S, Cetin-Atalay R, Neri ML. Inhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation status.. Investigational new drugs. 2011 December ; 29 (6) : 1303-13. doi:10.1007/s10637-010-9486-3. Download
Mumcuoglu M, Bagislar S, Yuzugullu H, Alotaibi H, Senturk S, Telkoparan P, Gur-Dedeoglu B, Cingoz B, Bozkurt B, Tazebay UH, Yulug IG, Akcali KC, Ozturk M. The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity.. PloS one. 2010 June ; 5 (6) : e11288. doi:10.1371/journal.pone.0011288. Download
Senturk S, Mumcuoglu M, Gursoy-Yuzugullu O, Cingoz B, Akcali KC, Ozturk M. Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth.. Hepatology (Baltimore, Md.). 2010 September ; 52 (3) : 966-74. doi:10.1002/hep.23769. Download
Yuzugullu H, Benhaj K, Ozturk N, Senturk S, Celik E, Toylu A, Tasdemir N, Yilmaz M, Erdal E, Akcali KC, Atabey N, Ozturk M. Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells.. Molecular cancer. 2009 October ; 8 : 90. doi:10.1186/1476-4598-8-90. Download
Ozturk M, Arslan-Ergul A, Bagislar S, Senturk S, Yuzugullu H. Senescence and immortality in hepatocellular carcinoma.. Cancer letters. 2009 December ; 286 (1) : 103-13. doi:10.1016/j.canlet.2008.10.048. Download
Ozturk N, Erdal E, Mumcuoglu M, Akcali KC, Yalcin O, Senturk S, Arslan-Ergul A, Gur B, Yulug I, Cetin-Atalay R, Yakicier C, Yagci T, Tez M, Ozturk M. Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells.. Proceedings of the National Academy of Sciences of the United States of America. 2006 February ; 103 (7) : 2178-83. doi:10.1073/pnas.0510877103. Download
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CRISPR/Cas9 Gene Editing in Mammalian Cells Using LentiCRISPRv2/LentiGuide-Puro Vectors (2021). CRISPR-Cas Methods. Springer Protocols.
Inducible CRISPR-based Genome Editing for the Characterization of Cancer Genes (2018). Genome Editing and Engineering: From TALENs, ZFNs and CRISPRs to Molecular Surgery. Cambridge University Press.
Total : 2