The molecular mechanisms of drug resistance of glioblastoma. Part 3. Differentiation and apoptosis of glioblastoma cells

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Abstract

Glioblastomas are one of the most malignant and frequent human tumors, characterized by rapid growth, metastasis, resistance to therapy and the formation of relapses. The formation of multidrug resistance mechanisms in glioblastomas cells is often combined with inhibition of cell death and differentiation pathways and prevents an increase in the effectiveness of therapy in this group of patients. The review examines the relationship of molecular mechanisms of multidrug resistance with differentiation and apoptosis of glioblastomas with an emphasis on identifying new targets among proteins, microRNAs, suppressor genes, and oncogenes.

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About the authors

Alexander N. Chernov

Institute of Experimental Medicine

Author for correspondence.
Email: al.chernov@mail.ru
ORCID iD: 0000-0003-2464-7370
Scopus Author ID: 26649406700

PhD, Cand. Sci. (Biol.), Senior Research Associate, Department of General Pathology and Pathological Physiology

Russian Federation, Saint Petersburg

Elvira S. Galimova

Institute of Experimental Medicine; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: elvira8galimova@gmail.com
ORCID iD: 0000-0002-8773-0932
Scopus Author ID: 24331659400

PhD, Cand. Sci. (Biol.), Senior Research Associate of Interdisciplinary Laboratory for Neurobiology; Senior Research Associate, Department of General Pathology and Pathological Physiology

Russian Federation, Saint Petersburg; Saint Petersburg

Olga V. Shamova

Institute of Experimental Medicine; Saint Petersburg State University

Email: oshamova@yandex.ru
ORCID iD: 0000-0002-5168-2801
Scopus Author ID: 6603643804
ResearcherId: F-6743-2013

Dr. Sci. (Biol.), Assistant Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of General Pathology and Pathological Physiology; Professor of the Department of Biochemistry

Russian Federation, Saint Petersburg; Saint Petersburg

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2. Fig. 1. Signaling mechanisms of differentiation and MDR in glioblastomas. See text for explanations. The figure shows the membrane of a glioblastoma cell, with some receptors included in it (BMPR — Bone morphogenetic protein receptor; CDH1, EGFR, Notch receptor, SMO — smoothened, frizzled class receptor) and intracellular signal transmission pathways that activate or inhibit differentiation. c-Fos — is a 380 amino acid protein with a basic leucine zipper region for dimerisation and DNA-binding and a transactivation domain at C-terminus; DLL4 — Delta like canonical Notch ligand 4; JAK — Janus kinase; KLF4 — Krüppel-like factor 4 transcription factor; MAPKK (MAP2K1) — Mitogen-activated protein kinase kinase 1; MAPKKK — Mitogen activated protein kinase-like protein; NICD — Notch intracellular domain; RA — Retinoic acid; RAC (AKT1) — AKT serine/threonine kinase 1; RAF (ZHX2) — Zinc fingers and homeoboxes 2; RAS — Guanosine-nucleotide-binding single-subunit small GTPase; RPS6K — Ribosomal protein S6 kinase; SHH — Sonic hedgehog protein; SOS — Son of Sevenless is a guanine nucleotide exchange factor; VAV1 — VAV guanine nucleotide exchange factor 1; YAP1 — Yes-associated protein 1. The remaining designations of molecules are given in the list of abbreviations

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3. Fig. 2. Signaling mechanisms of apoptosis and MDR in glioblastomas See text for explanations. The figure shows the membrane of a glioblastoma cell, with some receptors included in it (EGFR, Frizzled — Frizzled related protein 1, IGFR1 — Insulin growth factor receptor 1, Jagged 1, Notch receptor, SMO — Smoothened, frizzled class receptor, TGFR1 — Transforming growth factor beta receptor 1) and intracellular signal transmission pathways that activate or inhibit apoptosis. AC — acetyl group; APC — APC regulator of WNT signaling pathway; ATP — Adenosine triphosphate; AXIN1 — Axin 1; bCAT — Catenin-beta 1; Ca2+ — calcium; c-Fos — is a 380 amino acid protein with a basic leucine zipper region for dimerisation and DNA-binding and a transactivation domain at C-terminus; cAMP — Cyclic adenosine monophosphate; CCbL1 (KYAT1) — Kynurenine aminotransferase 1; CREB1 — cAMP responsive element binding protein 1; DAG — Diacylglycerol; DLL4 — Delta like canonical Notch ligand 4; Dv1 (IFT81) — Intraflagellar transport 81; E2F4, 5 — E2F transcription factor 4, -5; GBP (LGALS1) — Galectin 1; GSK3B — Glycogen synthase kinase 3 beta; IRS1 — Insulin receptor substrate 1; JAK — Janus kinase; KLF4 — Krüppel-like factor 4 transcription factor; MAPKK (MAP2K1) — Mitogen-activated protein kinase kinase 1; MAPKKK — Mitogen activated protein kinase-like protein; NICD — Notch intracellular domain; PIP2 — Phosphatidylinositol 4,5-bisphosphate; PIP3 — Phosphatidylinositol (3,4,5)-trisphosphate; PKC — Protein kinase C; RA — Retinoic acid; RAC (AKT1) — AKT serine/threonine kinase 1; RAF (ZHX2) — Zinc fingers and homeoboxes 2; RAS — Guanosine-nucleotide-binding single-subunit small GTPase; RhoA — RAS homolog family member A; ROCK — Rho-associated protein kinase; RPS6K — Ribosomal protein S6 kinase; SHH — Sonic hedgehog protein; SOS — Son of Sevenless is a guanine nucleotide exchange factor; Sp1 — Sp1 transcription factor; TCF4 — Basic helix-loop-helix transcription factor 4 also known as immunoglobulin transcription factor 2 (ITF-2); VAV1 — Vav guanine nucleotide exchange factor 1; YAP1 — Yes-associated protein 1; Yb1 (YBX1) — Y-box binding protein 1. The remaining designations of molecules are given in the list of abbreviations

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