Browsing by Subject "Cadherin"

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Open Access
Investigation of spontaneous differentiation of neural stem cells on synthetic scaffolds
(2017-08) Uyan, İdil
Despite the increasing incidents of brain injuries and neurodegenerative diseases, a definitive clinical therapy for these conditions has not been found yet. Nervous system injuries result in loss of neural cells, causing loss of function in the neural circuitry. As mature neurons do not divide, it is not possible to tolerate the loss of neurons by the production of new ones. In the central nervous system, even though neural stem cells are present, their number and regenerative capacity are very low. In addition, inhibitory molecules are released at the degeneration site which hinders reconnection of the remaining cells. As the damage is due to the loss of neurons, cell therapy is considered as a promising option. Neural stem cells are capable of differentiating into the three major cell types in the central nervous system: neurons, astrocytes, and oligodendrocytes. However, due to low rate of survival of the transplanted cells, there is still a need for a cell vehicle system to promote their survival, adhesion, migration, and differentiation. On the other hand, use of biological molecules such as growth factors or extracellular matrix proteins as vehicle systems should be minimized due to the immunological risks. Nanotechnological approaches serve as a great opportunity to mimic the native environment of the cells. Peptide amphiphiles (PAs) are self-assembling molecules that provide precise control over their secondary structure and the amino acid sequence, which can mimic proteins and show hydrogel properties. In this thesis, self-assembling PA scaffolds that mimic laminin, heparan sulfate and cadherin, which are key players in nervous system regeneration, have been investigated as cell delivery vehicles. Neurospheres are great models for studying the behavior of neural stem cells within a heterogeneous 3-dimensional cell population. Migration and differentiation behavior of neurospheres were investigated on laminin (LN), heparan sulfate (GAG), and cadherin-mimetic (HAV) PA nanofiber scaffolds. The results indicated that LN and GAG mimicking PA scaffolds cooperatively enhanced the migration of neurospheres, whereas cadherin mimetic PA scaffolds were individually sufficient to promote their migration. Also, a fine neural network was observed to be established on HAV-PA. These scaffolds hold high potential to be used as cell delivery vehicles.
Open Access
Metastasis suppressor proteins in cutaneous squamous cell carcinoma
(Elsevier, 2016-07) Bozdogan, O.; Vargel, I.; Cavusoglu, T.; Karabulut, A. A.; Karahan, G.; Sayar, N.; Atasoy, P.; Yulug, I. G.
Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.
Open Access
miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance
(Springer Verlag, 2016-06) Mutlu, M.; Raza, U.; Saatci, Ö.; Eyüpoğlu, E.; Yurdusev, E.; Şahin, Ö.
MicroRNAs (miRNAs) are 20–22-nucleotide small endogenous non-coding RNAs which regulate gene expression at post-transcriptional level. In the last two decades, identification of almost 2600 miRNAs in human and their potential to be modulated opened a new avenue to target almost all hallmarks of cancer. miRNAs have been classified as tumor suppressors or oncogenes depending on the phenotype they induce, the targets they modulate, and the tissue where they function. miR-200c, an illustrious tumor suppressor, is one of the highly studied miRNAs in terms of development, stemness, proliferation, epithelial-mesenchymal transition (EMT), therapy resistance, and metastasis. In this review, we first focus on the regulation of miR-200c expression and its role in regulating EMT in a ZEB1/E-cadherin axis-dependent and ZEB1/E-cadherin axis-independent manner. We then describe the role of miR-200c in therapy resistance in terms of multidrug resistance, chemoresistance, targeted therapy resistance, and radiotherapy resistance in various cancer types. We highlight the importance of miR-200c at the intersection of EMT and chemoresistance. Furthermore, we show how miR-200c coordinates several important signaling cascades such as TGF-β signaling, PI3K/Akt signaling, Notch signaling, VEGF signaling, and NF-κB signaling. Finally, we discuss miR-200c as a potential prognostic/diagnostic biomarker in several diseases, but mainly focusing on cancer and its potential application in future therapeutics.