Growth Factor Signaling in Cancer
Ayşim Güneş, Postdoctoral Fellow
Erkan Kahraman, Postdoctoral Fellow
Hande Topel, PhD Student
Yeliz Yılmaz, PhD Student
Ezgi Bağırsakçı, MSc Student
Mesude Angın, MSc Student
Dehan Çömez, MSc Student
Gülsün Bağcı, MSc Student
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Hepatocyte growth factor (HGF)/c-Met signaling is particularly important in the development of HCC as it controls growth, survival, migration and differentiation of tumor cells. Others and we have shown that abnormalities in HGF/c-Met signaling are implicated in tumor development and progression in a variety of cancers. The increase in c-Met expressing stem/progenitor cells in the liver is required for hepatocarcinogenesis, and high c-Met expression is correlated with metastasis, poor prognosis, and drug resistance. An elevated HGF level is uncommon in tumorigenesis except for breast tumors. Therefore, ligand-independent c-Met activation in HCC is a critical phenomenon that should be investigated further.
Our group is focused on signaling pathways that modulate the growth, motility, and invasion of hepatocellular carcinoma and using this molecular knowledge to improve the diagnosis and treatment of HCC. Our aim is to understand the molecular mechanisms behind the aggressive behavior and drug resistance in HCC and to translate this molecular knowledge to improve diagnosis and treatment.
Currently, our projects encompass:
1) The molecular mechanisms of HGF/c-Met mediated invasion and metastasis in HCC,
2) The effects of tumor microenvironment on the regulation of signaling networks and cellular behaviors of HCC,
3) The roles of non-coding RNAs in the regulation of c-Met signaling in HCC,
4) Fabrication and validation of a new lab-on-a-chip device for early diagnosis of metastasis.
In the next 5 years, we aim to:
• Identify the role of HGF/c-Met signaling in the regulation of glucose metabolism in HCC and further use this knowledge for developing strategies to prevent HCC.
• Understand the functional role of the HGF/c-Met axis in acquired sorafenib resistance in HCC cells and to improve targeted therapies of HCC patients.
• Fabricate and validate a Lab-on-a-chip (LOC) system that can predict the metastatic and invasive ability to circulate tumor cells (CTCs) in HCC and that can also determine the effects of drugs on tumor metastasis.
Atabey lab is currently seeking highly motivated PhD students. If interested, please contact email@example.com
Full list and citations : Google Scholar : Nese Atabey
• İşcan E, Güneş A, Korhan P, Yılmaz Y, Erdal E, Atabey N. The regulatory of heparin on c-Met signaling in hepatocellular carcinoma cells. J Cell Commun Signal. 2016 Dec 14. [Epub ahead of print]
• Saygideger-Kont Y, Minas TZ, Jones H, Hour S, Celik H, Temel I, et al. Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non-Small Cell Lung Cancer Cells. Neoplasia. 2016;18(2):111-20. doi: 10.1016/j.neo.2016.01.002. PubMed PMID: 26936397; PubMed Central PMCID: PMCPMC5005263.
• Firtina Karagonlar Z, Koc D, Sahin E, Avci ST, Yilmaz M, Atabey N, et al. Effect of adipocyte-secreted factors on EpCAM+/CD133+ hepatic stem cell population. Biochemical and biophysical research communications. 2016;474(3):482-90. doi: 10.1016/j.bbrc.2016.04.137. PubMed PMID: 27131739.
• Firtina Karagonlar Z, Koc D, Iscan E, Erdal E, Atabey N. Elevated HGF Expression as an Autocrine c-Met Activation Mechanism in Acquired Resistance to Sorafenib in HCC Cells. Cancer Sci. 2016 Jan 20. doi: 10.1111/cas.12891.
• Karagonlar ZF, Korhan P, Atabey N. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma. Drug Dev Res. 2015 Nov;76(7):357-67. doi: 10.1002/ddr.21274.
• Gunes A, Iscan E, Topel H, Avci ST, Gumustekin M, Erdal E, Atabey N. Heparin treatment increases thioredoxin interacting protein expression in hepatocellular carcinoma cells. Int J Biochem Cell Biol. 2015; 65:169-8.
• Korhan P, Erdal E, Kandemiş E, Cokaklı M, Nart D, Yılmaz F, Can A, Atabey N. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma. PLoS One. 2014; 9(8): e105278.
• Korhan P, Erdal E, Atabey N. miR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility, invasion and branching-morphogenesis by directly targeting c-Met. Biochem Biophys Res Commun. 2014; 450 (4):1304-12.
• Bozkaya G, Korhan P, Cokakli M, Erdal E, Sagol O, Karademir S, Korch C, Atabey N. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis. Mol Cancer. 2012;11: 64.
• Ozen E, Gozukizil A, Erdal E, Uren A, Bottaro DP, Atabey N. Heparin inhibits Hepatocyte Growth Factor induced motility and invasion of hepatocellular carcinoma cells through early growth response protein 1. PLoS One. 2012;7:e42717.
• Kunter I, Erdal E, Nart D, Yilmaz F, Karademir S, Sagol O, Atabey N. Active form of AKT controls cell proliferation and response to apoptosis in hepatocellular carcinoma. Oncol Rep. 2014;31(2):573-80.
• Gumustekin M, Kargi A, Bulut G, Gozukizil A, Ulukus C, Oztop I, Atabey N. HGF/c-Met overexpressions, but not met mutation, correlates with progression of non-small cell lung cancer. Pathol Oncol Res. 2012 (2):209-18.
• Bottaro, D. P., Giubellino A., Atabey S. N., Soriano J. V., Breckenridge D. E.ve Burke T. R. (2011). Inhibition of cell motility, angiogenesis, and metastasis, Pub No: US7871981 B2.
• Atabey, S. N., Bottaro D. P., Breckenridge D. E., Gao Y., Soriano J. V.ve Yao Z. J. (2001). Inhibition of cell motility and angiogenesis by inhibitors of the Grb2 SH2-domain, Pub No: WO2001028577 A3.