Browsing by Author "Sahin, Eren"

Now showing 1 - 2 of 2

Citation - WoS: 14
Citation - Scopus: 14
Effect of Adipocyte-Secreted Factors on Epcam+/Cd133+hepatic Stem Cell Population
(Academic Press Inc Elsevier Science, 2016) Karagonlar, Zeynep Firtina; Koc, Dogukan; Sahin, Eren; Avci, Sanem Tercan; Yilmaz, Mustafa; Atabey, Nese; Erdal, Esra
Recent epidemiological studies have associated obesity with a variety of cancer types including HCC. However, the tumor initiating role of obesity in hepatocarcinogenesis is still unknown. The objective of this paper is to investigate the effect of adipocyte-secreted factors on EpCAM+/CD133+ cancer stern cells and to identify which factors play a role in modulating hepatic cancer stem cell behavior. Our results demonstrated that adipocyte-secreted factors affect motility and drug resistance of EpCAM+/CD133+ cells. When incubated with adipocyte conditioned media, EpCAM-F/CD133+ cells exhibited augmented motility and reduced sorafenib-induced apoptosis. Using array-based system, we identified secretion of several cytokines such as IL6, IL8 and MCP1 by cultured adipocytes and activation of c-Met, STAT3 and ERK1/2 signaling pathways in EpCAM-F/CD133+ cells incubated with adipocyte conditioned media. Treating EpCAM+/CD133+ cancer stem cells with IL6 receptor blocking antibody or c-Met inhibitor SU11274 both reduced the increase in motility; however SU11274 had greater effect on relieving protection from sorafenib-induced apoptosis. These results indicate that adipocyte-secreted factors might regulate cancer stem cell behavior through several signaling molecules including c-Met, STAT3 and ERK1/2 and inhibition of these signaling pathways offer novel strategies in targeting the effect of adipose derived cytokines in cancer. (C) 2016 Elsevier Inc. All rights reserved.
Citation - WoS: 52
Citation - Scopus: 52
A Novel Function for Klf4 in Modulating the De-Differentiation of Epcam(-)/Cd133(-) Nonstem Cells Into Epcam(+)/Cd133(+) Liver Cancer Stem Cells in Hcc Cell Line Huh7
(Mdpi, 2020) Karagonlar, Zeynep Firtina; Akbari, Soheil; Karabiçici, Mustafa; Sahin, Eren; Avci, Sanem Tercan; Ersoy, Nevin; Ates, Kivilcim Eren
The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM(+)/CD133(+) liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM(-)/CD133(-) non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of beta -CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM(-)/CD133(-) non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM(-)/CD133(-) non-stem cells attained an in vivo tumor forming ability comparable to EpCAM(+)/CD133(+) LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM(+)/CD133(+) LCSCs in HuH7 HCC cells.