Serif Senturk

Serif Senturk
Dokuz Eylül University | DEÜ · Izmir Biomedicine and Genome Center

PhD

About

71
Publications
29,894
Reads
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3,212
Citations
Additional affiliations
November 2010 - October 2015
Cold Spring Harbor Laboratory
Position
  • PostDoc Position
September 2003 - July 2010
Bilkent University
Position
  • PhD Student
Education
October 2003 - July 2010
Bilkent University
Field of study
  • Cancer Biology
September 1998 - July 2003
Boğaziçi University
Field of study
  • Molecular Biology and Genetics

Publications

Publications (71)
Article
Full-text available
Senescence induction could be used as an effective treatment for hepatocellular carcinoma (HCC). However, major senescence inducers (p53 and p16Ink4a) are frequently inactivated in these cancers. We tested whether transforming growth factor-β (TGF-β) could serve as a potential senescence inducer in HCC. First, we screened for HCC cell lines with in...
Article
Full-text available
Significance p53 is one of the most intensively studied tumor-suppressor genes. We identified a naturally occurring p53 isoform, generated by an alternative-splicing event, that, although lacking transcriptional activity and canonical tumor suppressor functions, is able to reprogram cells toward the acquisition of metastatic features via a cyclophi...
Article
Full-text available
The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing...
Article
Full-text available
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surg...
Article
Full-text available
Cellular senescence is a state of stable cell cycle arrest that can be triggered in response to various insults and is characterized by distinct morphological hallmarks, gene expression profiles, and the senescence-associated secretory phenotype (SASP). Importantly, cellular senescence is a key component of normal physiology with tumor suppressive...
Chapter
Cancer remains a significant challenge in modern medicine, prompting continuous exploration for novel therapeutic strategies. Understanding the complex molecular mechanisms driving cancer progression is essential for developing effective treatments. The RUVBL1/2 complex, formed by highly conserved AAA+ ATPases (ATPases associated with diverse cellu...
Preprint
Full-text available
Hepatic fibrogenesis is a pathological outcome of chronic liver injury, characterized by the excessive accumulation of extracellular matrix proteins, leading to hepatocarcinogenesis. However, the lack of reliable models that mimic precancerous fibrogenesis in the early stage of the disease remains a significant obstacle. Here, we utilized human plu...
Article
Full-text available
The highly mutated nature of bladder cancers harboring mutations in chromatin regulatory genes opposing Polycomb-mediated repression highlights the importance of targeting EZH2 in bladder cancer. Furthermore, the critical role of the retinoic acid signaling pathway in the development and homeostasis of the urothelium, and the anti-oncogenic effects...
Article
The enzyme steroid type II 5-alpha-reductase (SRD5α2) is responsible for the conversion of testosterone to dihydrotestosterone (DHT), which is involved in prostate cancer, benign prostatic hyperplasia, and androgenic alopecia. Inhibition of SRD5α2 activity has been explored and presented as a potential treatment for these conditions, but current dr...
Chapter
H19 is a long non-coding RNA (lncRNA) molecule that is encoded by the H19 gene located on chromosome 11 in humans and is exclusively expressed from the maternal allele. H19 is involved in the regulation of various cellular and biological processes, including embryonic development, cell growth, and differentiation. The H19 gene has been implicated i...
Preprint
Emerging evidence has highlighted the importance of targeting EZH2 in bladder cancer owing to the highly mutated nature of bladder cancers harboring mutations in chromatin regulatory genes opposing Polycomb-mediated repression. Besides, enhanced expression of EZH2 contributes to pathogenesis. Furthermore, the critical role of the retinoic acid sign...
Article
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, therapeutic management of HCC remains a challenge, emphasizing the importance of exploring novel targets. MALT1 paracaspase is a druggable signaling molecule who...
Article
Full-text available
Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based vaccines are easier and cheaper to produce and do not require special storage/transportation conditions, they are suitable for low-/middle-income countries. Here, we report our vaccine development studies with the receptor binding...
Article
Full-text available
Epigenetic deregulation is a critical theme which needs further investigation in bladder cancer research. One of the most highly mutated genes in bladder cancer is KDM6A, which functions as an H3K27 demethylase and is one of the MLL3/4 complexes. To decipher the role of KDM6A in normal versus tumor settings, we identified the genomic landscape of K...
Article
Full-text available
Bladder cancer is mostly present in the form of urothelium carcinoma, causing over 150,000 deaths each year. Its histopathological classification as muscle invasive (MIBC) and non-muscle invasive (NMIBC) is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape o...
Article
TGF-β signaling mediates its biological effects by engaging canonical Smad proteins and crosstalking extensively with other signaling networks, including the NF-kB pathway. The paracaspase MALT1 is an intracellular signaling molecule essential for NF-kB activation downstream of several key cell surface receptors. Despite intensive research on TGF-β...
Article
Full-text available
The isocitrate dehydrogenase (IDH), which participates in the TCA cycle, is an important key enzyme in regulating cell metabolism. The effect of the metabolic IDH enzyme on cancer pathogenesis has recently been shown in different types of cancer. However, the role of wild-type (wt) IDH1 in the development of colon cancer is still unknown. Our study...
Preprint
Epigenetic deregulation is a critical theme which needs further investigation for bladder cancer research. One of the highly mutated genes in bladder cancer is KDM6A, functioning as a H3K27 demethylase and is part of the MLL3/4 complexes. To decipher the role of KDM6A in normal versus tumor setting, we identified the genomic landscape of KDM6A in n...
Chapter
Full-text available
Non-small cell lung cancer (NSCLC), the most common form of lung cancer, accounts for 85% of all new lung cancer cases and is the leading cause of cancer-related death worldwide. NSCLC histosubtypes include adenocarcinoma, large-cell carcinoma, and squamous cell carcinoma. Cancer driving mechanisms for some NSCLC adenocarcinomas involve activating...
Preprint
Full-text available
Deregulation of glycolysis is common in non-small cell lung cancer (NSCLC). Hexokinase (HK) enzymes catalyze the phosphoryl-group-transfer in glucose metabolism. There are a very few studies that have begun to reveal the connections between glucose metabolism and splicing programs. Unlike HK2 gene, which is expressed as a single transcript, there a...
Article
Full-text available
Ongoing research efforts to identify potent regulatory sequences that deliver robust and sustained transgene expression are critical for Chinese hamster ovary (CHO) cell line development technologies to meet the growing demand for recombinant proteins. Here we report the engineering and validation of a highly customizable single vector toolkit that...
Article
Full-text available
Hepatocellular carcinoma (HCC) is associated with genetic and nongenetic aberrations that impact multiple genes and pathways, including the frequently dysregulated transforming growth factor β (TGF-β) signaling pathway. The regulatory cytokine TGF-β and its signaling effectors govern a broad spectrum of spatiotemporally regulated molecular and cell...
Article
Full-text available
AXL, a member of the TAM family, is a promising therapeutic target due to its elevated expression in advanced hepatocellular carcinoma (HCC), particularly in association with acquired drug resistance. Previously, RNA interference was used to study its role in cancer, and several phenotypic changes, including attenuated cell proliferation and decrea...
Article
Full-text available
Background Hepatocellular carcinoma (HCC) is one of the most challenging malignancies, with high morbidity and mortality rates. The transforming growth factor-β (TGF-β) pathway plays a dual role in HCC, acting as both tumor suppressor and promoter. A thorough understanding of the mechanisms underlying its opposing functions is important. The growth...
Preprint
Bladder cancer is mostly present in the form of urothelium carcinoma, causing over 150.000 deaths each year. Its histopathological classification as muscle invasive (MIBC) and non-muscle invasive (NMIBC) is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape o...
Article
Full-text available
Hepatocellular carcinoma (HCC) is an aggressive, chemo resistant neoplasm with poor prognosis and limited treatment options. Exploring activated pathways upon drug treatment can be used to discover more effective anticancer agents to overcome therapy resistance and enhance therapeutic outcomes for patients with advanced HCC. Human tumor-derived cel...
Chapter
Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has revolutionized the field of genome engineering, medicine, as well as biotechnology. CRISPR/Cas9 is a form of bacterial defense mechanism that can be used for editing genomes by targeting a 20-nucleotide sequence using a guide RNA and nuclease enzyme called Cas9 en...
Article
Full-text available
Despite current advancements in research and therapeutics, lung cancer remains the leading cause of cancer-related mortality worldwide. This is mainly due to the resistance that patients develop against chemotherapeutic agents over the course of treatment. In the context of non-small cell lung cancers (NSCLC) harboring EGFR oncogenic mutations, aug...
Article
Aim: The CRISPR/Cas9 system is a promising gene-editing tool for various anticancer therapies; however, development of a biocompatible, nonviral and efficient delivery of CRISPR/Cas9 expression systems remains a challenge. Materials & methods: Solid lipid nanoparticles (SLNs) were produced based on pseudo and 3D ternary plots. Obtained SLNs and the...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
Despite current advancements in research and therapeutics, lung cancer remains the leading cause of cancer-related mortality worldwide. Many lung cancer patients will develop resistance to chemotherapeutics. In the context of non-small cell lung cancers harboring EGFR oncogenic mutations, augmented levels of AXL and GAS6 have been found to drive Er...
Article
Full-text available
Retinoic acid (RA) signaling is a crucial developmental pathway involved in urothelium development, differentiation and regeneration. Deregulation of the RA signaling is highly implicated in several cancers, including bladder cancer, underlying the need to unravel the complete regulatory aspects of the retinoids in bladder tumorigenesis. Given the...
Article
Full-text available
“Liver medicine” refers to all diagnostic and treatment strategies of diseases and conditions that cause liver failure directly or indirectly. Despite significant advances in the field of liver medicine in recent years, improved tools are needed to efficiently define the pathophysiology of liver diseases and provide effective therapeutic options to...
Article
Full-text available
Background: Considerable evidence suggests that oxidative stress plays an essential role in the progression of hepatocellular carcinoma (HCC). While acquired resistance to oxidative stress is the main driver of aggressive cell phenotype, the underlying mechanisms remain unknown. Here, we tested the hypothesis that elevated expression of Thioredoxin...
Chapter
Genome Editing and Engineering - edited by Krishnarao Appasani August 2018
Data
Supplementary Figures and Supplementary Tables
Article
Full-text available
We identified an error in figure 3F with the labelling of cell lines. The error might have appeared from figure 5C which has a very similar outline for labelling the cell lines. We have provided the corrected figure 3 below. (Image Presented). The article has been corrected accordingly.
Data
Values of p53 mRNA expression with different mutations obtained from four different tumor types. DOI: http://dx.doi.org/10.7554/eLife.17929.031
Data
Number of tumor samples with indicated mutation types in primary and metastatic colorectal carcinoma. DOI: http://dx.doi.org/10.7554/eLife.17929.032
Data
List of tumor studies used for analysis of distribution of Missense, Exon-6 and other truncations in TP53. DOI: http://dx.doi.org/10.7554/eLife.17929.030
Data
Sequence of sense strand of shRNAs used in this study. DOI: http://dx.doi.org/10.7554/eLife.17929.033
Data
Complimentary oligonucleotides used for cloning the indicated sgRNAs. DOI: http://dx.doi.org/10.7554/eLife.17929.034
Article
Full-text available
TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally an...
Patent
Provided herein are methods and compositions for inhibiting epithelial to mesenchymal transition of a cell.
Article
The sporadic transition from indolent to metastatic disease is a hallmark of prostate cancer (PC) and frequently involves deletion of PTEN and TP53. We recently recapitulated metastasis of Pten/ Trp53-mutant PC in mouse using the RapidCaP system and surprisingly, we found that it is driven by Myc, rather than Akt activation. Here, we show that cell...
Article
Full-text available
The Cas9/CRISPR system is a powerful tool for studying gene function. Here we describe a method that allows temporal control of Cas9/CRISPER activity based on conditional CAS9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 enables conditional rapid and reversible Cas9 expression in vitro and efficient gen...
Article
Full-text available
We have recently recapitulated metastasis of human PTEN/ TP53-mutant PC in mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by Myc-, and not Akt-activation. Here, we show that cell-cell communication by Il6 drives the Akt-Myc switch through activation of the Akt-suppressing phosphatase Phlpp2, when Pten and p53...
Article
Full-text available
Telomerase is a cellular ribonucleoprotein reverse transcriptase that plays a crucial role in telomere maintenance. This enzyme is expressed in approximately 90% of human tumors, but not in the majority of normal somatic cells. imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'→P5' thio-phosphoramidate lipid conjugate, which represents th...
Article
The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is involved in cell survival and anti-apoptotic signaling. Akt has been shown to be constitutively expressed in a variety of human tumors including hepatocellular carcinoma (HCC). In this report we analyzed the status of Akt pathway in three HCC cell lin...
Article
Full-text available
Targets of E2F transcription factors effectively regulate the cell cycle from worms to humans. Furthermore, the dysregulation of E2F transcription modules plays a highly conserved role in cancers of human and zebrafish. Studying E2F target expression under a given cellular state, such as quiescence, might lead to a better understanding of the conse...
Data
STR analysis data that shows the authenticity of breast cancer cell lines used in this study. (1.50 MB XLS)
Data
p16Ink4a expression in colonies obtained from breast cancer cell lines. There was no correlation between p16Ink4a expression and progenitor subtype. (3.39 MB TIF)
Data
Co-staining experiments indicate that SABG staining is associated with p21Cip1, but with p16Ink4a expression in SCP cells. Colonies were generated from T47D and MB-MDA-231 cells and subjected to SABG staining, followed by p21Cip1 or p16Ink4a immunoperoxidase (brown) staining. MDA-MB-231 cells were used as negative control. (2.74 MB TIF)
Data
Effect of estrogen receptor-overexpression on the production of BrdU-negative terminally arrested cell progeny. ER-overexpressing (ER-5, ER-7, ER-26) and control (C-8, C-10, C-11) stable clones were established from T47D cells. Following transfection with ER expression and control vectors, colonies were generated from respective cell lines, labeled...
Data
Unsupervised hierarchical clustering of breast tumor and cell line gene expression data that is described in Fig. 7A. Dendrogram shown here includes tumor and cell line sample IDs. (1.05 MB TIF)
Data
Gene clusters, genetic mutations and epigenetic changes of breast cancer cell lines used in this study. (0.05 MB DOC)
Data
Tumors derived from T47D but not from MDA-MB-231 display SABG (+) senescent cells. Two of four T47D tumors displayed SABG+ cells. All four MDA-MB-231 tumors lacked SABG+ cells. (7.97 MB TIF)
Data
Detection of SABG+ senescent cells in estrogen receptor-positive breast tumors. Snap-frozen tumors were used to obtain 6 µ thick sections and used directly to detect SABG+ cells. H&E: hematoxylin-eosin staining. (9.45 MB TIF)
Data
ASMA+ myoepithelial-like cells are produced frequently in senescent cell progenitor T47D and MCF-7 cell lines under confluent conditions. ASMA was tested by immunoperoxidase. (4.08 MB TIF)
Data
Estrogen receptor (ER) status, main pathological features of senescence staining (SABG) of breast tumors used in this study. (0.05 MB DOC)
Article
Full-text available
Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogene...
Article
Full-text available
Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to re...
Article
Full-text available
beta-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated i...
Article
Full-text available
Tumor cells have the capacity to proliferate indefinitely that is qualified as replicative immortality. This ability contrasts with the intrinsic control of the number of cell divisions in human somatic tissues by a mechanism called replicative senescence. Replicative immortality is acquired by inactivation of p53 and p16INK4a genes and reactivatio...

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