TY - JOUR AU - Gurbi, Bianka AU - Brauswetter, Diána AU - Pénzes, Kinga AU - Varga, Attila AU - Krenács, Tibor AU - Dános, Kornél AU - Birtalan, Ede AU - Tamás, László AU - Csala, Miklós TI - MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 3 PG - 19 SN - 1661-6596 DO - 10.3390/ijms24032782 UR - https://m2.mtmt.hu/api/publication/33610921 ID - 33610921 N1 - Export Date: 13 May 2023 AB - The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is often activated by overexpressed epidermal growth factor receptor (EGFR) and stimulates the progression of HNSCCs. Our research was performed on three human papillomavirus (HPV)-negative HNSCC-cell lines: Detroit 562, FaDu and SCC25. Changes in cell viability upon EGFR and/or MEK inhibitors were measured by the MTT method. The protein-expression and phosphorylation profiles of the EGFR-initiated signaling pathways were assessed using Western-blot analysis. The EGFR expression and pY1068-EGFR levels were also studied in the patient-derived HNSCC samples. We found significant differences between the sensitivity of the tumor-cell lines used. The SCC25 line was found to be the most sensitive to the MEK inhibitors, possibly due to the lack of feedback Akt activation through EGFR. By contrast, this feedback activation had an important role in the FaDu cells. The observed insensitivity of the Detroit 562 cells to the MEK inhibitors might have been caused by their PIK3CA mutation. Among HNSCC cell lines, EGFR-initiated signaling pathways are particularly versatile. An ERK/EGFR feedback loop can lead to Akt-pathway activation upon MEK inhibition, and it is related not only to increased amounts of EGFR but also to the elevation of pY1068-EGFR levels. The presence of this mechanism may justify the combined application of EGFR and MEK inhibitors. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Attila AU - Nguyen, Minh Tu AU - Pénzes, Kinga AU - Bátai, Bence AU - Gyulavári, Pál AU - Gurbi, Bianka AU - Murányi, József AU - Csermely, Péter AU - Csala, Miklós AU - Vántus, Tibor AU - Sőti, Csaba TI - Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 2 PG - 15 SN - 2073-4409 DO - 10.3390/cells12020212 UR - https://m2.mtmt.hu/api/publication/33541689 ID - 33541689 N1 - Department of Molecular Biology, Semmelweis University, Budapest, 1094, Hungary MTA-SE Pathobiochemistry Research Group, Semmelweis University, Budapest, 1094, Hungary Institute of Medical Microbiology, Semmelweis University, Budapest, 1089, Hungary HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, 1085, Hungary IQVIA Hungary, Budapest, 1117, Hungary Cited By :2 Export Date: 19 January 2024 Correspondence Address: Varga, A.; Department of Molecular Biology, Hungary; email: varga.attila@med.semmelweis-univ.hu Correspondence Address: Sőti, C.; Department of Molecular Biology, Hungary; email: soti.csaba@med.semmelweis-univ.hu AB - Prostate cancer metastasis is a significant cause of mortality in men. PKD3 facilitates tumor growth and metastasis, however, its regulation is largely unclear. The Hsp90 chaperone stabilizes an array of signaling client proteins, thus is an enabler of the malignant phenotype. Here, using different prostate cancer cell lines, we report that Hsp90 ensures PKD3 conformational stability and function to promote cancer cell migration. We found that pharmacological inhibition of either PKDs or Hsp90 dose-dependently abrogated the migration of DU145 and PC3 metastatic prostate cancer cells. Hsp90 inhibition by ganetespib caused a dose-dependent depletion of PKD2, PKD3, and Akt, which are all involved in metastasis formation. Proximity ligation assay and immunoprecipitation experiments demonstrated a physical interaction between Hsp90 and PKD3. Inhibition of the chaperone–client interaction induced misfolding and proteasomal degradation of PKD3. PKD3 siRNA combined with ganetespib treatment demonstrated a specific involvement of PKD3 in DU145 and PC3 cell migration, which was entirely dependent on Hsp90. Finally, ectopic expression of PKD3 enhanced migration of non-metastatic LNCaP cells in an Hsp90-dependent manner. Altogether, our findings identify PKD3 as an Hsp90 client and uncover a potential mechanism of Hsp90 in prostate cancer metastasis. The molecular interaction revealed here may regulate other biological and pathological functions. LA - English DB - MTMT ER - TY - JOUR AU - Yousef, M. AU - Szabó, Ildikó AU - Murányi, József AU - Illien, Françoise AU - Soltész, Dóra AU - Bató, Csaba AU - Tóth, Gabriella AU - Batta, Gyula Gábor (Ifj.) AU - Nagy, Péter AU - Sagan, Sandrine AU - Bánóczi, Zoltán TI - Cell-Penetrating Dabcyl-Containing Tetraarginines with Backbone Aromatics as Uptake Enhancers JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 1 PG - 20 SN - 1999-4923 DO - 10.3390/pharmaceutics15010141 UR - https://m2.mtmt.hu/api/publication/33538163 ID - 33538163 N1 - Department of Organic Chemistry, Eötvös L. University, Budapest, 1117, Hungary MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd Research Network (ELKH), Budapest, 1117, Hungary Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, 1094, Hungary MTA-SE, Pathobiochemistry Research Group, Budapest, 1094, Hungary Sorbonne Université, École Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, Paris, 75005, France Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary Department of Genetics and Applied Microbiology, Faculty of Science and Technology, University of Debrecen, Debrecen, 4032, Hungary Cited By :5 Export Date: 26 January 2024 Correspondence Address: Bánóczi, Z.; Department of Organic Chemistry, Hungary; email: zoltan.banoczi@ttk.elte.hu AB - Cell-penetrating peptides represent an emerging class of carriers capable of effective cellular delivery. This work demonstrates the preparation and investigation of efficient CPPs. We have already shown that the presence of 4-((4-(dimethylamino)phenyl)azo)benzoic acid (Dabcyl) and Trp greatly increase the uptake of oligoarginines. This work is a further step in that direction. We have explored the possibility of employing unnatural, aromatic amino acids, to mimic Trp properties and effects. The added residues allow the introduction of aromaticity, not as a side-chain group, but rather as a part of the sequence. The constructs presented exceptional internalization on various cell lines, with an evident structure–activity relationship. The CPPs were investigated for their entry mechanisms, and our peptides exploit favorable pathways, yet one of the peptides relies highly on direct penetration. Confocal microscopy studies have shown selectivity towards the cell lines, by showing diffuse uptake in FADU cells, while vesicular uptake takes place in SCC-25 cell line. These highly active CPPs have proved their applicability in cargo delivery by successfully delivering antitumor drugs into MCF-7 and MDA-MB-231 cells. The modifications in the sequences allow the preparation of short yet highly effective constructs able to rival the penetration of well-known CPPs such as octaarginine (Arg8). LA - English DB - MTMT ER - TY - JOUR AU - Czuczi, Tamás AU - Murányi, József AU - Bárány, Péter Tibor AU - Móra , István András AU - Borbély, Adina Noémi AU - Csala, Miklós AU - Csámpai, Antal TI - Synthesis and Antiproliferative Activity of Novel Imipridone–Ferrocene Hybrids with Triazole and Alkyne Linkers JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 15 PY - 2022 IS - 4 PG - 19 SN - 1424-8247 DO - 10.3390/ph15040468 UR - https://m2.mtmt.hu/api/publication/32782717 ID - 32782717 LA - English DB - MTMT ER - TY - PAT AU - Csámpai, Antal AU - Bárány, Péter Tibor AU - Czuczi, Tamas AU - Kovacs, Imre AU - Adamis, Balint AU - Nemeth, Zsofia AU - Murányi, József AU - Olahne, Szabo Rita AU - Bosze, Szilvia AU - Mezo, Gabor AU - Kőhidai, László AU - Lajkó, Eszter AU - Takács, Angéla AU - Láng, Orsolya AU - Mezo, Diana TI - Synthesis of novel imipridone derivatives and their evaluation for their anticancer activity.. WO2022029459A1 TS - WO2022029459A1 PY - 2022 SP - 91pp. PG - 91 UR - https://m2.mtmt.hu/api/publication/32683354 ID - 32683354 AB - The present invention relates to compds. of formula (I) (I) or pharmaceutically acceptable salts, and stereoisomers thereof, including enantiomers, racemic mixts., mixts. of enantiomers, or combinations thereof, which are applicable for use in treating cancer diseases. The present invention further relates to a pharmaceutical compn. comprising the above compds. [on SciFinder(R)] LA - English DB - MTMT ER - TY - JOUR AU - Bőgel, Gábor AU - Murányi, József AU - Szokol, Bálint AU - Kukor, Zoltán AU - Móra , István András AU - Kardon Tamás, Zoltán AU - Őrfi, László AU - Hrabák, András TI - Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages JF - HELIYON J2 - HELIYON VL - 8 PY - 2022 IS - 1 PG - 16 SN - 2405-8440 DO - 10.1016/j.heliyon.2021.e08670 UR - https://m2.mtmt.hu/api/publication/32574856 ID - 32574856 LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, András AU - Mihály, Judith AU - Wacha, András Ferenc AU - Németh, Csaba AU - Besztercei, Balázs AU - Gyulavári, Pál AU - Varga, Zoltán AU - Peták, István AU - Bóta, Attila TI - Combination of multifunctional ursolic acid with kinase inhibitors for anti-cancer drug carrier vesicles JF - MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS J2 - MAT SCI ENG C-MATER VL - 131 PY - 2021 PG - 11 SN - 0928-4931 DO - 10.1016/j.msec.2021.112481 UR - https://m2.mtmt.hu/api/publication/32461679 ID - 32461679 N1 - Research Centre for Natural Sciences - Eötvös Loránd Research Network, Institute of Materials and Environmental Chemistry, Research Group of Biological Nanochemistry, Magyar tudósok boulevard 2, Budapest, 1117, Hungary Semmelweis University, Institute of Clinical Experimental Research, Tűzoltó street 37-47, Budapest, 1094, Hungary Semmelweis University, Pathobiochemistry Research Group, Tűzoltó street 37-47, Budapest, 1094, Hungary University of Illinois at Chicago, Department of Biopharmaceutical Sciences, 833 S. Wood street, Chicago, IL 60612, United States Oncompass Medicine Ltd., Retek street 34, Budapest, 1024, Hungary Semmelweis University, Department of Pharmacology and Pharmacotherapy, Nagyvárad square 4, Budapest, 1089, Hungary Export Date: 26 October 2021 Correspondence Address: Mihály, J.; Research Centre for Natural Sciences - Eötvös Loránd Research Network, Magyar tudósok boulevard 2, Hungary; email: mihaly.judith@ttk.hu LA - English DB - MTMT ER - TY - CHAP AU - Kiss, Krisztina AU - Biri-Kovács, Beáta AU - Szabó, Rita (Oláhné) AU - Enyedi, Kata Nóra AU - Murányi, József AU - Schlosser, Gitta (Vácziné) AU - Ranđelović, I. AU - Tóvári, J. AU - Mező, Gábor ED - Mező, Gábor TI - Optimation of homing peptide sequence selected by phage display for HT-29 colon cancer cells to improve the antitumor activity T2 - Development of bioconjugates and their module constructs for targeted therapy of cancers with high mortality PB - Eötvös Loránd Tudományegyetem (ELTE) CY - Budapest SN - 9789634892861 PY - 2020 SP - 5 EP - 9 PG - 5 UR - https://m2.mtmt.hu/api/publication/31916954 ID - 31916954 LA - English DB - MTMT ER - TY - JOUR AU - Holczer, Marianna AU - Hajdú, Bence AU - Lőrincz, T. AU - Szarka, András AU - Bánhegyi, Gábor AU - Kapuy, Orsolya TI - Fine-tuning of AMPK–ULK1–mTORC1 regulatory triangle is crucial for autophagy oscillation JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 10 PY - 2020 IS - 1 PG - 12 SN - 2045-2322 DO - 10.1038/s41598-020-75030-8 UR - https://m2.mtmt.hu/api/publication/31643674 ID - 31643674 N1 - Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Tűzoltó utca 37-47, Budapest, 1094, Hungary Laboratory of Biochemistry and Molecular Biology, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Budapest, Hungary Pathobiochemistry Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary Cited By :3 Export Date: 1 October 2021 Correspondence Address: Kapuy, O.; Department of Medical Chemistry, Tűzoltó utca 37-47, Hungary; email: kapuy.orsolya@med.semmelweis-univ.hu Chemicals/CAS: germinal center kinase; mammalian target of rapamycin complex 1; mammalian target of rapamycin complex 2; NIMA related kinase 1; oncogene protein v akt; oncogene protein v raf; protein kinase, 9026-43-1; rapamycin, 53123-88-9; serine threonine protein kinase ULK1; serine/threonine protein kinase WNK1; AMP-activated protein kinase kinase; Autophagy-Related Protein-1 Homolog; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Mechanistic Target of Rapamycin Complex 1; Protein Kinases; Sirolimus; ULK1 protein, human Funding details: STIA-18-KF Funding details: Semmelweis Egyetem Funding text 1: The authors are thankful to M. Márton. This work was supported by the Baron Munchausen Program of the Department of Medical Chemistry, Molecular Biology and Pathobiochemistry of Semmelweis University, Budapest, by the ÚNKP-19-3-I-SE-81 New National Excellence Program of the Ministry for Innovation and Technology, by a STIA-18-KF and a STIA-20-KF of Semmelweis University. AB - Autophagy is an intracellular digestive process, which has a crucial role in maintaining cellular homeostasis by self-eating the unnecessary and/or damaged components of the cell at various stress events. ULK1, one of the key elements of autophagy activator complex, together with the two sensors of nutrient and energy conditions, called mTORC1 and AMPK kinases, guarantee the precise function of cell response mechanism. We claim that the feedback loops of AMPK–mTORC1–ULK1 regulatory triangle determine an accurate dynamical characteristic of autophagic process upon cellular stress. By using both molecular and theoretical biological techniques, here we reveal that a delayed negative feedback loop between active AMPK and ULK1 is essential to manage a proper cellular answer after prolonged starvation or rapamycin addition. AMPK kinase quickly gets induced followed by AMPK-P-dependent ULK1 activation, whereas active ULK1 has a rapid negative effect on AMPK-P resulting in a delayed inhibition of ULK1. The AMPK-P → ULK1 ˧ AMPK-P negative feedback loop results in a periodic repeat of their activation and inactivation and an oscillatory activation of autophagy, as well. We demonstrate that the periodic induction of self-cannibalism is necessary for the proper dynamical behaviour of the control network when mTORC1 is inhibited with respect to various stress events. By computational simulations we also suggest various scenario to introduce “delay” on AMPK-P-dependent ULK1 activation (i.e. extra regulatory element in the wiring diagram or multi-phosphorylation of ULK1). © 2020, The Author(s). LA - English DB - MTMT ER - TY - JOUR AU - Hajdinák, Péter AU - Szabó, Melinda AU - Kiss, Emese AU - Veress, Lili AU - Wunderlich, Lívius AU - Szarka, András TI - Genetic Polymorphism of GSTP-1 Affects Cyclophosphamide Treatment of Autoimmune Diseases JF - MOLECULES J2 - MOLECULES VL - 25 PY - 2020 IS - 7 PG - 12 SN - 1420-3049 DO - 10.3390/molecules25071542 UR - https://m2.mtmt.hu/api/publication/31314893 ID - 31314893 LA - English DB - MTMT ER -