of 36.6 and 26.5 M on osteosarcoma and GBM cells, respec-l tively. PD also induced the percentage of apoptotic cell death through the activation of ROS and caspase 3/7 signaling in these cancerous cells. Moreover, cell cycle analysis and transcriptome profiling are performed to understand the action of mechanism of PD on cancerous cells. The ability of targeting GBM stem cells (GSCs) and resistance GSCs of PD compared with temo-zolomide. Our study hopes to provide insight into mechanism of action of phenolic derivatives and the results suggest that alky-laminophenols may represent a new class of therapeutic agents in the management of bone and brain cancers.
P-35-085
The role of TKS5 in the invadopodia
formation, endocytosis, plasma membrane
remodeling and actin cytoskeleton
reorganization
Y. Nemesh, S. Kropyvko , A. Rynditch*
Institute of Molecular Biology and Genetics NASU, 150 Zabolotnogo St., Kyiv 03143, Ukraine
TKS5 is a critical component of invadopodia as its absence results in the loss of cancer cells ability to form these invasive structures. This fact makes TKS5 a potential target for the can-cer cure and one of the central proteins in the investigation of cancer cell invasion. Additionally, the question remains about the function of TKS5 in normal cells. Therefore, in order to extend knowledge about TKS5 role in healthy and invasive cells, we tested the TKS5 interaction with 50-inositol-phosphatase SHIP2; the protein involved in plasma membrane remodeling: AMPH1, BIN1, CIN85, ITSN1, ITSN2; the protein involved in the actin cytoskeleton rearrangement: CR16, WIRE, CTTN; the proteins involved in signal transduction: PLC 1, SRC, CRK,c CSK; and another scaffold protein TKS4. We used the GST Pull-down assay to identify the protein-protein interaction. We revealed that TKS5 interacts with SHIP2. TKS5 near the plasma membrane can recruit SHIP2, which provides local increasing of phosphatidylinositol-3,4-bisphosphate with subsequently TKS5 secondary involvement that binds invadopodia initiation protein complex. We have shown the TKS5 interaction with TKS4 that may realize on a stage of invadopodia maturation. We identified the TKS5 interaction with the neuron-specific SH3A domain of ITSN1, ITSN2, AMPH1, BIN1, CIN85, CTTN, CR16, and WIRE, that may appoint its role in plasma membrane remodel-ing, endocytosis, and actin cytoskeleton rearrangement. It is sig-nificant that AMPH1 and BIN1 may act as negative regulators of invadopodia initiation. Their interaction with TKS5 proline motifs can prohibit the formation of the invadopodia initiation complex on the scaffold of TKS5. Noticeably that TKS5 estab-lishes the triple complex with WIRE and b-actin, however, TKS5 interacts with CR16 without b-actin. Hence, TKS5 may modulate actin cytoskeleton rearrangement depending on the binding partner. *The authors marked with an asterisk equally contributed to the work.
P-35-086
Sera levels of homoarginine, homocysteine
and ischemia modified albumin in patients
with breast cancer
F. Kosova1, S. Abus¸oglu2
, €O. K. Beksac¸3, G. Tekin4, B. C¸etin3, A. Sepici Dinc¸el5, Z. Arı6, A. €Unl€u2
1Department of Biochemistry, Celal Bayar University School of Health Services, Manisa, Turkey,2Department of Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey,3Dr. Abdurrahman Yurtaslan Oncology Hospital, Ankara, Turkey, 4Department of Biochemistry, Selc¸uk University School of Health Services, Konya, Turkey,5Department of Medical Biochemistry, Gazi University Faculty of Medicine, Ankara, Turkey, 6Department of Biochemistry, Celal Bayar University Faculty of Medicine, Manisa, Turkey
Aim: L-homoarginine is formed from lysine by arginine glycine amidinotransferase (AGAT) and is mainly produced in the kid-ney. It has been shown to increase nitric oxide (NO) production by inhibiting either arginase or protein arginine methyltrans-ferases (PRMTs). Thus, increased L-homoarginine concentrations might exert a positive effect on endothelial function. The aim of this study was to determine whether there was a change in serum levels of homoarginine, homocysteine and ischemia modified albumin in patients with breast cancer. Methods: Twenty-seven early stage breast cancer patients and 27 healthy controls were selected for this study. Blood samples were collected preopera-tively and postoperapreopera-tively from cancer patients. Participants with known systemic diseases, including cardiovascular disease, renal disease, gastrointestinal disease, pulmonary disease, acute infec-tion, chronic inflammation were excluded. Serum homoarginine levels were analyzed with API 3200 AB SCIEX LC-MS/MS sys-tem. Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively), NG monomethyl-L-arginine (L-NMMA), L-Arginine and L-Citrulline levels were measured with Liquid chromatography-tandem mass spectrometry. SDMA/ADMA and Arginine/ADMA ratios are calculated. Preoperative values were compared against healthy controls and postoperative values. Results: Serum homoarginine levels were significantly decreased but Serum IMA levels were increased and there was no difference for serum homocysteine levels in group 1 compared to group 2 (P <0.001), respectively. Conclusions: Homoarginine and IMA are potentially useful diagnostic biomarkers for breast cancer diagnosis. Besides, Homoarginine and IMA can be useful biomarkers for breast cancer follow-up.
P-35-087
Alpha-catulin as a marker of a specific
population of invasive breast cancer cells
M. Gielata, K. Karpinska, V. Vassilev, A. Kobielak Centre of New Technologies, Warszawa, Poland
Breast cancer is the most commonly diagnosed cancer in women worldwide. The epithelial-to-mesenchymal transition (EMT) has been associated with breast cancer progression. However tran-sient, reversible nature of EMT and the fact that only a small minority of carcinoma cells may undergo an EMT in primary tumours makes observing an EMTin vivo a great challenge. In our previous studies, we observed that the upregulation of catulin expression correlates with the transition of tumour cells from epithelial to mesenchymal morphology. Therefore we developed a reporter system, Catulin-GFP that allows us for the first time to isolate and characterize in vivo a small population of invasive breast cancer cells from the xenograft model and test their cancer initiating potential. We used two triple negative breast cancer cell lines, MDA231, and HCC1806 that show high expression of
Posters
Cell signaling in tumor biology
345 FEBS Open Bio9(Suppl. 1) (2019) 65–431 DOI: 10.1002/2211-5463.12675
ª2019 The Authors. FEBS Open Bioª2019 FEBS
Prnted by [Selcuk Unverstes - 193.255.247.064 - /do/epdf/10.1002/221
