Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

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Citation - WoS: 48
Citation - Scopus: 48
5-Fluorouracil Signaling Through a Calcium-Calmodulin Pathway Is Required for P53 Activation and Apoptosis in Colon Carcinoma Cells
(Nature Publishing Group, 2013-09) Can, G.; Akpınar, B.; Baran, Yusuf; Zhivotovsky, B.; Olsson, M.; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca 2+) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca 2+ through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca 2+ -chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53 -/- cells confirmed the importance of a Ca 2+ -CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes. © 2013 Macmillan Publishers Limited.
Citation - WoS: 7
Citation - Scopus: 6
Addition of Exogenous Diacylglycerol Enhances Wnt/Β-catenin Signaling Through Stimulation of Macropinocytosis
(Elsevier, 2023) Azbazdar, Yağmur; Tejeda-Munoz, Nydia; Monka, Julia C.; Dayrit, Alex; Binder, Grace; De Robertis, Edward M.; Özhan, Güneş; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Activation of Wnt signaling triggers macropinocytosis and drives many tumors. We now report that the exogenous addition of the second messenger lipid sn-1,2 DAG to the culture medium rapidly induces macropinocytosis. This is accompanied by potentiation of the effects of added Wnt3a recombinant protein or the glycogen synthase kinase 3 (GSK3) inhibitor lithium chloride (LiCl, which mimics Wnt signaling) in luciferase transcriptional reporter assays. In a colorectal carcinoma cell line in which mutation of adenomatous polyposis coli (APC) causes constitutive Wnt signaling, DAG addition increased levels of nuclear β-catenin, and this increase was partially inhibited by an inhibitor of macropinocytosis. DAG also expanded multivesicular bodies marked by the tetraspan protein CD63. In an in vivo situation, microinjection of DAG induced Wnt-like twinned body axes when co-injected with small amounts of LiCl into Xenopus embryos. These results suggest that the DAG second messenger plays a role in Wnt-driven cancer progression. © 2023 The Author(s)
Citation - WoS: 64
Citation - Scopus: 81
Advanced Backcross Qtl Analysis of a Lycopersicon Esculentum X L. Pennellii Cross and Identification of Possible Orthologs in the Solanaceae
(Springer Verlag, 2004-02) Frary, Anne; Fulton, Theresa M.; Zamir, Dani; Tanksley, Steven D.; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
In this study, the advanced backcross QTL (AB-QTL) mapping strategy was used to identify loci for yield, processing and fruit quality traits in a population derived from the interspecific cross Lycopersicon esculentum E6203 x Lycopersicon pennellii accession LA1657. A total of 175 BC2 plants were genotyped with 150 molecular markers and BC2F1 plots were grown and phenotyped for 25 traits in three locations in Israel and California, U.S.A. A total of 84 different QTLs were identified, 45% of which have been possibly identified in other wild-species-derived populations of tomato. Moreover, three fruit-weight/size and shape QTLs (fs2b.1, fw3.1/fsz3.1 andfs8.1) appear to have putative orthologs in the related solanaceous species, pepper and eggplant. For the 23 traits for which allelic effects could be deemed as favorable or unfavorable, 26% of the identified loci had L. pennellii alleles that enhanced the performance of the elite parent. Alleles that could be targeted for further introgression into cultivated tomato were also identified.
Advantage of Co-Culture Strategy for Targeted Cancer Treatment and in Vitro Studies
(Elsevier, 2021) Ulu, Gizem Tuğçe; Bayram, Nazende Nur; Dinçer İşoğlu, Sevil; Baran, Yusuf; 01.01. Units Affiliated to the Rectorate; 04.03. Department of Molecular Biology and Genetics; 01. Izmir Institute of Technology; 04. Faculty of Science
Breast cancer tissues include carcinoma cells and stromal cells, and intra-tumoral stroma that consists of different types of cells. For this point, cell-cell interaction and communication have a potential role in cancer progression. Mono-cell culture is used for cancer treatment approaches. However, cell-cell interaction and communication can not be evaluated on mono-culture cells. So, co-culture models provide low-cost screening to determine cell proliferation for drug application before moving forward to in vivo models. Also, determination of cell morphology in co culture system is critical to understand advantages.
Citation - WoS: 2
Citation - Scopus: 2
Analysis of Est-Ssrs in Silver Birch (betula Pendula Roth.)
(Northeast Forestry University, 2016-06) Filiz, Ertuğrul; Doğan, İlhan; Özyigit, İbrahim İlker; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Simple sequence repeats (SSRs) defined as sequence repeat units between 1 and 6 bp occur abundantly in both coding and non-coding regions in eukaryotic genomes and these repeats can affect gene expression. In this study, ESTs (expressed sequence tags) of Betula pendula (silver birch) were analyzed for in silico mining of EST-SSRs, protein annotation, open reading frames (ORFs), designing primers, and identifying codon repetitions. In B. pendula, the frequency of ESTs containing SSRs was 7.8 % with an average of 1SSR/4. 78 kb of EST sequences. A total of 188 SSRs was identified by using MISA software and di-nucleotide SSR motifs (65.9 %) were found to be the most abundant type of repeat motif followed by tri- (27.1 %), tetra- (4.8 %), and penta- (2.2 %) motifs. Based on ORF analysis, 175 of 178 sequences were predicted as ORFs and the most frequent SSRs were detected in 5′ UTR (58.43 %), followed by in ORF (31.46 %) and in 3′ UTR (8.43 %). 102 of 178 ESTs were annotated as ribosomal protein, transport protein, membrane protein, carrier protein, binding protein, and transferase protein. For a total of 102 SSRs (57.3 %) with significant matches, a set of 102 primers (100 %) with forward and reverse strands was designed by using Primer3 software. Serine (Ser, 19.6 %) was predominant in putative encoded amino acids and most of amino acids showed nonpolar (35.3 %) nature. Our data provide resources for B. pendula and can be useful for in silico comparative analyses of Betulaceae species, including SSR mining.
Citation - WoS: 131
Citation - Scopus: 137
Antagonistic Roles of Notch and P63 in Controlling Mammary Epithelial Cell Fates
(Nature Publishing Group, 2010-10) Yalçın Özuysal, Özden; Fiche, M.; Guitierrez, M.; Wagner, K. U.; Raffoul, W.; Brisken, C.; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
The breast epithelium has two major compartments, luminal and basal cells, that are established and maintained by poorly understood mechanisms. The p53 homolog, p63, is required for the formation of mammary buds, but its function in the breast after birth is unknown. We show that in primary human breast epithelial cells, maintenance of basal cell characteristics depends on continued expression of the p63 isoform, ΔNp63, which is expressed in the basal compartment. Forced expression of ΔNp63 in purified luminal cells confers a basal phenotype. Notch signaling downmodulates ΔNp63 expression and mimics ΔNp63 depletion, whereas forced expression of ΔNp63 partially counteracts the effects of Notch. Consistent with Notch activation specifying luminal cell fate in the mammary gland, Notch signaling activity is specifically detected in mice at sites of pubertal ductal morphogenesis where luminal cell fate is determined. Basal cells in which Notch signaling is active show decreased p63 expression. Both constitutive expression of ΔNp63 and ablation of Notch signaling are incompatible with luminal cell fate. Thus, the balance between basal and luminal cell compartments of the breast is regulated by antagonistic functions of ΔNp63 and Notch. © 2010 Macmillan Publishers Limited All rights reserved.
Citation - WoS: 61
Citation - Scopus: 77
Anti-Proliferative, Apoptotic and Signal Transduction Effects of Hesperidin in Non-Small Cell Lung Cancer Cells
(Springer Verlag, 2015-06-29) Çinçin, Zeynep Birsu; Ünlü, Miray; Kıran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Çakmakoğlu, Bedia; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Purpose: Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. Methods: The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). Results: We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-κB signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. Conclusions: Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.
Citation - WoS: 66
Citation - Scopus: 80
Antimicrobial and Antioxidant Activities of Turkish Extra Virgin Olive Oils
(American Chemical Society, 2010-07) Karaosmanoğlu, Hande; Soyer, Ferda; Özen, Banu; Tokatlı, Figen; 04.03. Department of Molecular Biology and Genetics; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
Turkish extra virgin olive oils (EVOO) from different varieties/ geographical origins and their phenolic compounds were investigated in terms of their antimicrobial and antioxidant properties in comparison to refined olive, hazelnut, and canola oils. Antimicrobial activity was tested against three foodborne pathogenic bacteria, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella Enteritidis. Although all EVOOs showed a bactericidal effect, the individual phenolic compounds demonstrated only slight antimicrobial activity. Moreover, refined oil samples did not show any antimicrobial activity. Among the phenolic compounds, cinnamic acid (2 mg/kg of oil) had the highest percent inhibition value with 0.25 log reduction against L. monocytogenes. The synergistic interactions of tyrosol, vanillin, vanillic, and cinnamic acids were also observed against Salmonella Enteritidis. The antioxidant activities of oils were tested by β-carotene-linoleate model system and ABTS method. In both methods, EVOOs showed higher antioxidant activities, whereas refined oils had lower activity. The ABTS method provided a higher correlation (0.89) with total phenol content. © 2010 American Chemical Society.
Citation - WoS: 124
Citation - Scopus: 154
Antimicrobial and Antioxidant Activity of Edible Zein Films Incorporated With Lysozyme, Albumin Proteins and Disodium Edta
(Elsevier Ltd., 2007-01) Mecitoğlu Güçbilmez, Çiğdem; Yemenicioğlu, Ahmet; Arslanoğlu, Alper; 04.03. Department of Molecular Biology and Genetics; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
In this study, partially purified lysozyme was incorporated into zein films in combination with chickpea albumin extract (CPAE), bovine serum albumin (BSA) and disodium EDTA. The zein films showed an inherent free radical scavenging activity. Incorporation of lysozyme did not contribute to soluble free radical scavenging activity of zein films. However, the incorporation of lysozyme in combination with CPAE increased the soluble and immobilized free radical scavenging activity of zein films 17% to 25% and almost 84%, respectively. The incorporation of CPAE also improved the distribution of partially purified lysozyme preparation in zein films and enabled the controlled release of lysozyme by reducing its release rate from zein films between 1.5- and 3.5-fold, depending on the concentration of incorporated CPAE. In contrast, the BSA incorporation made distribution of lysozyme more heterogeneous and it did not contribute to the free radical scavenging activity of films significantly. The combinational incorporation of partially purified lysozyme with disodium EDTA · 2H2O or CPAE and disodium EDTA · 2H2O gave zein films effective on Escherichia coli and Bacillus subtilis. This study clearly showed the benefits of using functional protein extracts to control lysozyme distribution and release rate and to improve antioxidant activity in zein films.
Citation - WoS: 14
Citation - Scopus: 15
Authentication of Botanical Origin in Herbal Teas by Plastid Noncoding Dna Length Polymorphisms
(American Chemical Society, 2015-07-01) Uncu, Ali Tevfik; Uncu, Ayşe Özgür; Frary, Anne; Doğanlar, Sami; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
The aim of this study was to develop a DNA barcode assay to authenticate the botanical origin of herbal teas. To reach this aim, we tested the efficiency of a PCR-capillary electrophoresis (PCR-CE) approach on commercial herbal tea samples using two noncoding plastid barcodes, the trnL intron and the intergenic spacer between trnL and trnF. Barcode DNA length polymorphisms proved successful in authenticating the species origin of herbal teas. We verified the validity of our approach by sequencing species-specific barcode amplicons from herbal tea samples. Moreover, we displayed the utility of PCR-CE assays coupled with sequencing to identify the origin of undeclared plant material in herbal tea samples. The PCR-CE assays proposed in this work can be applied as routine tests for the verification of botanical origin in herbal teas and can be extended to authenticate all types of herbal foodstuffs.
Citation - WoS: 45
Citation - Scopus: 54
Barcode Dna Length Polymorphisms Vs Fatty Acid Profiling for Adulteration Detection in Olive Oil
(Elsevier Ltd., 2017-04) Uncu, Ali Tevfik; Uncu, Ayşe Özgür; Frary, Anne; Doğanlar, Sami; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
The aim of this study was to compare the performance of a DNA-barcode assay with fatty acid profile analysis to authenticate the botanical origin of olive oil. To achieve this aim, we performed a PCR-capillary electrophoresis (PCR-CE) approach on olive oil: seed oil blends using the plastid . trnL (UAA) intron barcode. In parallel to genomic analysis, we subjected the samples to gas chromatography analysis of fatty acid composition. While the PCR-CE assay proved equally efficient as gas chromatography analysis in detecting adulteration with soybean, palm, rapeseed, sunflower, sesame, cottonseed and peanut oils, it was superior to the widely utilized analytical chemistry approach in revealing the adulterant species and detecting small quantities of corn and safflower oils in olive oil. Moreover, the DNA-based test correctly identified all tested olive oil: hazelnut oil blends whereas it was not feasible to detect hazelnut oil adulteration through fatty acid profile analysis. Thus, the present research has shown the feasibility of a PCR-CE barcode assay to detect adulteration in olive oil.
Citation - WoS: 8
Citation - Scopus: 10
Bioactive Sphingolipids in Docetaxel-Induced Apoptosis in Human Prostate Cancer Cells
(Elsevier Ltd., 2012-03) Başsoy, Esen Yonca; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
In this study, we examined the possible roles of ceramide/sphingosine-1-phosphate and ceramide/glucosyleceramide signaling in docetaxel-induced apoptosis by examining expression levels of the glucosyleceramide synthase and sphingosine kinase-1 and ceramide synthase gene family. As confirmed by isobologram analysis, docetaxel in combination with agents that increase intracellular ceramide levels increased the cytotoxic and apoptotic effects of docetaxel synergistically. More importantly, RT-PCR results revealed that expression levels of glucosyleceramide synthase and sphingosine kinase-1 were downregulated and ceramide synthase genes were upregulated in response to docetaxel. This study identifies mechanisms underlying the involvement of ceramide metabolizing genes in docetaxel-induced apoptosis in prostate cancer cells. © 2012 Elsevier Masson SAS.
Citation - WoS: 49
Citation - Scopus: 66
Bioactive, Functional and Edible Film-Forming Properties of Isolated Hazelnut (corylus Avellana L.) Meal Proteins
(Elsevier Ltd., 2014-05) Aydemir, Levent Yurdaer; Adan Gökbulut, Aysun; Baran, Yusuf; Yemenicioğlu, Ahmet; 04.03. Department of Molecular Biology and Genetics; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
This study aimed characterization of bioactive, functional and edible film making properties of isolated proteins from untreated (HPI), hot extracted (HPI-H), acetone washed (HPI-AW), and acetone washed and hot extracted (HPC-AW-H) hazelnut meals. The most bioactive protein extract was HPC-AW-H, followed by HPI-AW, HPI-H and HPI, based on antioxidant activity (TEAC and ORAC: 158-461mmolTrolox/kg), iron chelation (60.7-126.7mmolEDTA/kg), angiotensin-converting enzyme inhibition (IC50: 0.57-1.0mg/mL) and antiproliferative activity on colon cancer cells (IC50: 3.0-4.6mg/ml). Protein contents of HPI, HPI-H and HPI-AW (93.3-94.5%) were higher than that of HPC-AW-H (86.0%), but HPC-AW-H showed the best pH-solubility profile. The extracts showed good oil absorption (7.4-9.4g/g) and foaming, but limited water holding and gelling capacities, and emulsion stability. The protein extracts gave transparent, yellowish to brownish and reddish colored and water soluble edible films. The HPI gave the lightest colored films with acceptable mechanical properties (elongation up to 144% and tensile strength up to 4.9MPa). 1-D and 2-D electrophoresis clearly showed the molecular and isoelectric profiles of hazelnut proteins. The overall results of this study showed that the bioactive, solubility and gelation properties of hazelnut proteins could be improved by simple processes like acetone washing and/or heat treatment. The hazelnut proteins are valuable as multipurpose food ingredients.
Citation - WoS: 27
Citation - Scopus: 44
Biodiversity, Drug Discovery, and the Future of Global Health: Introducing the Biodiversity To Biomedicine Consortium, a Call To Action
(Edinburgh University Global Health Society, 2017-11) Neergheen-Bhujun, Vidushi; Awan, Almas Taj; Baran, Yusuf; Bunnefeld, Nils; Chan, Kit; Dela Cruz, Thomas Edison; Egamberdieva, Dilfuza; Elsasser, Simon; Johnson, Mari-Vaughn V.; Komai, Shoji; Konevega, Andrey L.; Malone, John H.; Mason, Paul; Nguon, Rothsophal; Piper, Ross; Shrestha, Uttam Babu; Pesic, Milica; Kagansky, Alexander; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Looking to nature for medicine is nothing new – we have been doing it for tens of thousands of years and although modern pharmaceutical science has come a long way from those ancient roots, nature is and will always be an important source of useful compounds and inspiration. Dismissing nature in this regard is a huge mistake as evolution is the greatest problem solver and the myriad compounds produced by the immense variety of species we share the planet with have been honed by three billion years of trial and error. However, with every bit of habitat that disappears under the plough or concrete we impoverish nature and deprive ourselves of potential medicines.
Citation - WoS: 20
Citation - Scopus: 31
Biodiversity: the Overlooked Source of Human Health
(Elsevier, 2023-03) Linhares, Yuliya; Kaganski, Alexander; Agyare, Christian; Aksan Kurnaz, Işıl; Neergheen, Vidushi; Kolodziejczyk, Bartlomiej; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Biodiversity is the measure of the variation of lifeforms in a given ecological system. Biodiversity provides ecosystems with the robustness, stability, and resilience that sustains them. This is ultimately essential for our survival because we depend on the services that natural ecosystems provide (food, fresh water, air, climate, and medicine). Despite this, human activity is driving an unprecedented rate of biodiversity decline, which may jeopardize the life-support systems of the planet if no urgent action is taken. In this article we show why biodiversity is essential for human health. We raise our case and focus on the biomedicine services that are enabled by biodiversity, and we present known and novel approaches to promote biodiversity conservation.
Citation - WoS: 7
Citation - Scopus: 10
Biotechnology for Enhanced Nutritional Quality in Plants
(Taylor and Francis Ltd., 2013-09) Uncu, Ayşe Özgür; Doğanlar, Sami; Frary, Anne; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
With almost 870 million people estimated to suffer from chronic hunger worldwide, undernourishment represents a major problem that severely affects people in developing countries. In addition to undernourishment, micronutrient deficiency alone can be a cause of serious illness and death. Large portions of the world population rely on a single, starch-rich crop as their primary energy source and these staple crops are generally not rich sources of micronutrients. As a result, physical and mental health problems related to micronutrient deficiencies are estimated to affect around two billion people worldwide. The situation is expected to get worse in parallel with the expanding world population. Improving the nutritional quality of staple crops seems to be an effective and straightforward solution to the problem. Conventional breeding has long been employed for this purpose but success has been limited to the existing diversity in the gene pool. However, biotechnology enables addition or improvement of any nutrient, even those that are scarce or totally absent in a crop species. In addition, biotechnology introduces speed to the biofortification process compared to conventional breeding. Genetic engineering was successfully employed to improve a wide variety of nutritional traits over the last decade. In the present review, progress toward engineering various types of major and minor constituents for the improvement of plant nutritional quality is discussed. © 2013 Copyright Taylor and Francis Group, LLC.
Brain Lipid Profile of Early Onset Tay-Sachs Disease Mouse Model
(Springernature, 2020) Şengül, Tuğçe; Can, Melike; Akyıldız Demir, Seçil; Klose, C.; Surma, M.; Seyrantepe, Volkan; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
[Abstract Not Available]
Citation - WoS: 18
Citation - Scopus: 19
Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop
(Elsevier, 2021) Önal, Sevgi; Türker Burhan, Merve; Batı Ayaz, Gizem; Yanık, Hamdullah; Pesen Okvur, Devrim; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Breast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. While both BCC and macrophages showed invasion/chemotaxis to fetal bovine serum, only macrophages showed chemotaxis to BCC in custom designed 3D cell-on-a-chip devices. These results were in agreement with gradient simulation results and ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. Therefore, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively. © 2020 Elsevier Ltd
Citation - WoS: 6
Citation - Scopus: 6
Canonical Wnt and Tgf-β/Bmp Signaling Enhance Melanocyte Regeneration but Suppress Invasiveness, Migration, and Proliferation of Melanoma Cells
(Frontiers Media S.A., 2023) Katkat, Esra; Demirci, Yeliz; Heger, Guillaume; Karagülle, Doğa; Papatheodorou, Irene; Brazma, Alvis; Özhan, Güneş; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology
Melanoma is the deadliest form of skin cancer and develops from the melanocytes that are responsible for the pigmentation of the skin. The skin is also a highly regenerative organ, harboring a pool of undifferentiated melanocyte stem cells that proliferate and differentiate into mature melanocytes during regenerative processes in the adult. Melanoma and melanocyte regeneration share remarkable cellular features, including activation of cell proliferation and migration. Yet, melanoma considerably differs from the regenerating melanocytes with respect to abnormal proliferation, invasive growth, and metastasis. Thus, it is likely that at the cellular level, melanoma resembles early stages of melanocyte regeneration with increased proliferation but separates from the later melanocyte regeneration stages due to reduced proliferation and enhanced differentiation. Here, by exploiting the zebrafish melanocytes that can efficiently regenerate and be induced to undergo malignant melanoma, we unravel the transcriptome profiles of the regenerating melanocytes during early and late regeneration and the melanocytic nevi and malignant melanoma. Our global comparison of the gene expression profiles of melanocyte regeneration and nevi/melanoma uncovers the opposite regulation of a substantial number of genes related to Wnt signaling and transforming growth factor beta (TGF-beta)/(bone morphogenetic protein) BMP signaling pathways between regeneration and cancer. Functional activation of canonical Wnt or TGF-beta/BMP pathways during melanocyte regeneration promoted melanocyte regeneration but potently suppressed the invasiveness, migration, and proliferation of human melanoma cells in vitro and in vivo. Therefore, the opposite regulation of signaling mechanisms between melanocyte regeneration and melanoma can be exploited to stop tumor growth and develop new anti-cancer therapies.
A Carbohydrate sulfotransferase mutant zebrafish shows importance of keratan sulfate proteoglycan in skeletal structure
(Mary Ann Liebert, 2024) Basol, M.; Ersoz, E.; Özaktaş, Helin; Cakan-Akdogan, G.; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology

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