AG Signal Transduction in Cancer
Main research topics:
- Studies on the functional role of the PI3K/Akt/mTOR pathway in cancer and circulating tumor cells (CTCs).
- Development of combination therapies with AKT and mTOR inhibitors in preclinical studies in hepatocellular carcinoma, breast carcinoma and head and neck tumors
- Identification of molecular mechanisms that may lead to the emergence of therapy resistance
- Identification of biomarkers to predict recurrent liver metastases in colorectal carcinoma
- Development of micro-bioreactors (lab-on-a-chip) for quantitative analysis of specific inhibitors in 3D tumor cultures (tumoroids) (cooperation with Prof. Trieu, Institute of Microsystems Engineering, TU Hamburg-Harburg)
- Studies on the functional role of SHIP1 as a tumor suppressor of leukemogenesis and carcinogenesis in solid tumor entities
- Structural analysis of the inositol-5-phosphatase SHIP1 as well as of patient-derived SHIP1 mutants and their role as oncogenes in carcinogenesis (cooperation with Prof. Kirchmair, Center for Bioinformatics, University of Hamburg and Dr. Witt, CSSB/DESY)
The PI3K/AKT/mTOR pathway as a druggable molecular target in circulating tumor cells (Supervision: Dr. Daniel J. Smit / Prof. Dr. Manfred Jücker)
Circulating tumor cells (CTCs) are cells that have lost the adhesion to the primary tumor and circulate in the peripheral blood. Recent research suggests that circulating tumor cells are the initiators of metastasis formation and therefore a noteworthy target for new therapeutic strategies. The PI3K/AKT/mTOR signaling pathway was shown to be often hyperactivated in cancer. Activation of the pathway leads to proliferation, angiogenesis, reduced apoptosis, epithelial-mesenchymal transition and increased metastatic potential. Many possible targets for inhibition inside the pathway have been identified in the past, including the key proteins AKT and mTOR.
In our most recent publication (Smit et al., 2020), we analyzed in cooperation with the groups of Prof. Catherine Alix-Panabières (Laboratory of Rare Human Circulating Cells, University Medical Center of Montpellier) and Prof. Klaus Pantel (Department of Tumor Biology, University Medical Center Hamburg-Eppendorf) the functional role of the PI3K/AKT/mTOR signaling pathway in the circulating tumor cell line ‘CTC-MCC-41’ derived from a patient with colorectal cancer. We could demonstrate that this cell line is susceptible to AKT and mTOR inhibition using MK2206 and RAD001 within the nanomolar range. Stable AKT isoform specific knockdowns of AKT1 and AKT2 significantly impaired proliferation of this cell line. These data demonstrate that the PI3K/AKT/mTOR signaling pathway plays a key role in the proliferation of CTC-MCC-41 cells and suggests that specific inhibition of this pathway in CTCs may be a promising approach to inhibit metastasis.
Selected recent contributions:
Smit, D.J.; Pantel, K.; Jücker, M. Circulating tumor cells as a promising target for individualized drug susceptibility tests in cancer therapy. Biochemical Pharmacology 2021, 188, 114589, doi: 10.1016/j.bcp.2021.114589.
Smit, D. J., Cayrefourcq, L., Haider, M.-T., Hinz, N., Pantel, K., Alix-Panabières, C., Jücker, M. High Sensitivity of Circulating Tumor Cells Derived from a Colorectal Cancer Patient for Dual Inhibition with AKT and mTOR Inhibitors. Cells 2020, 9, 2129. doi: 10.3390/cells9092129.
Koch, C.; Kuske, A.; Joosse S. A.; Yigit, G.; Sflomos, G.; Thaler, S.; Smit, D.J.; Werner, S.; Borgmann, K.; Gärtner, S.; Mossahebi Mohammadi, P.; Battista, L.; Cayrefourcq, L.; Altmüller, J.; Salinas-Riester, G.; Raithatha, K.; Zibat, A.; Goy, Y.; Ott, L.; Bartkowiak, K.; Tan, T. Z.; Zhou, Q.; Speicher, M. R.; Müller, V.; Gorges, T. M.; Jücker, M.; Thiery, J.-P.; Brisken, C.; Riethdorf, S.; Alix-Panabières, C.; Pantel, K. Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity. EMBO Mol. Med. 2020, 12, e11908. doi: 10.15252/emmm.201911908.
Isoform-specific effects of AKT in breast cancer bone metastasis (Supervision: Prof. Dr. Manfred Jücker)
Breast cancer is the most common cancer in women and the development of bone metastasis is associated with poor prognosis and impaired survival. AKT, also known as protein kinase B, is a key regulator of cellular processes and plays a crucial role in breast cancer bone metastasis. AKT consists of three isoforms (i.e., AKT1, AKT2 and AKT3). These isoforms demonstrated in some extend different effects on signal transduction of cancer cells. Thus, we are investigating the role of AKT isoforms on breast cancer cells e.g. on proliferation, migration, chemotaxis and bone metastasis in a mouse model by stable sh-RNA-mediated isoform-specific knockdowns of AKT isoforms in bone-seeking sublines of breast cancer cells. Our purpose is, to get further insights into AKT-isoform mediated signal transduction in bone metastasis and reveal clinical implications for AKT-isoform inhibition in breast cancer treatment.
Selected recent contributions
Hinz, N.; Jücker, M. AKT in Bone Metastasis of Solid Tumors: A Comprehensive Review. Cancers (Basel) 2021, 13, 2287, doi:10.3390/cancers13102287.
Hinz, N.; Baranowsky, A.; Horn, M.; Kriegs, M.; Sibbertsen, F.; Smit, D.J.; Clezardin, P.; Lange, T.; Schinke, T.; Jücker, M. Knockdown of AKT3 Activates HER2 and DDR Kinases in Bone-Seeking Breast Cancer Cells, Promotes Metastasis In Vivo and Attenuates the TGFβ/CTGF Axis. Cells 2021, 10, 430, doi:10.3390/cells10020430.
Hinz, N.; Jücker, M. Distinct functions of AKT isoforms in breast cancer: a comprehensive review. Cell Commun Signal 2019, 17, 154, doi:10.1186/s12964-019-0450-3.
Analysis of SHIP1 as a tumor suppressor of leukemogenesis
The PI3-kinase/AKT pathway is constitutively activated in approximately 50-70% of patients with acute myeloid leukemia (AML) and mediates both proliferation promoting and anti-apoptotic signals. The inositol 5-phosphatase SHIP1 is a negative regulator of the PI3K/AKT signaling pathway in hematopoietic cells (Helgason et al., 1998, Li et al., 1999). In our group, we are investigating the functional role of SHIP1 in leukemogenesis.
We have shown that restoration of SHIP1 expression in the human T cell line Jurkat leads to decreased proliferation by prolonging the G1 phase of the cell cycle (Horn, et al 2004) and that vector-mediated overexpression of SHIP1 in CD34+ cells from AML patients reduces proliferation of these cells in vitro (Metzner, et al 2009). In a xenograft mouse model, we demonstrated that overexpression of SHIP1 in the human AML cell line UKE-1 leads to prolonged mouse survival after transplantation into NSG mice (Täger 2017).
A hallmark of tumor suppressors is their mutational inactivation in cells. Various mutations have also been found for the SHIP1-encoding gene INPP5D in AML patients. Our group was able to show that some of these SHIP1 mutations have a strongly reduced enzymatic activity and can no longer negatively regulate the PI3K/AKT signaling pathway (Brauer, et al 2012) thereby also losing their tumor suppressing effect on the growth of human AML cells in a xenograft mouse model (Täger et al 2017).
We have now identified phosphorylation of SHIP1 at tyrosine residue 1021 by SRC family tyrosine kinases as the molecular mechanism for inactivation of SHIP1, which can lead to proteasomal degradation of SHIP1 and thus to its inactivation (Ehm et al, unpublished data). In further studies using an inducible leukemia mouse model, we will now investigate the role of SHIP1 as a tumor suppressor in the initiation and development of AML in vivo by deleting SHIP1 in multipotent hematopoietic stem and progenitor cells. In addition, we plan to identify the underlying signaling pathways by gene expression studies.
3R-Project (BMBF): Reduction of animal experiments in preclinical studies for the analyis of drugs for individualized cancer therapy by using in vitro methods with tumor tissues (tumoroids) (Projektleitung Prof. Dr. Manfred Jücker)
In the current application, we will analyze the possibility to reduce animal experiments in drug testing by using an in vitro method to predict drug sensitivity. Tumor cells from patients with colorectal cancer (CRC) will be analyzed for the effect of distinct drugs in a xenotransplantation mouse model (PDX) in comparison to the effect of the same drugs analyzed in in vitro assays. For this purpose, we will analyze patients with synchronous hepatic metastasis after written consent and with approved ethic vote. In the in vitro assays we will analyze proliferation, vitality, apoptosis, migration, invasion and three dimensional tumoroid growth. These data will be compared with the growth of the primary tumor after subcutaneous transplantation in the mice. The drugs analyzed in this project will be FOLFOX, a combination of the substances 5-Fluoruracil, Folic acid und Oxaliplatin which are applied intravenously in patients. This so called FOLFOX regime is the current state of the art therapy for patients with colorectal cancer.
If any of these in vitro methods will give comparable results to the mouse experiments, this method can be used to replace at least partially some of the many animal experiments currently performed in drug screening.
Training
- Project studies (for molecular life sciences students)
- bachelor theses
- master theses
- doctoral theses (PhD, Dr. rer. nat., Dr. med., Dr. med. dent., Dr. rer. biol. hum.)
- Internship
Publications Jücker Group
2024
K-Ras(V12) differentially affects the three Akt isoforms in lung and pancreatic carcinoma cells and upregulates E-cadherin and NCAM via Akt3
Geißert R, Lammert A, Wirth S, Hönig R, Lohfink D, Unger M, Pek D, Schlüter K, Scheftschik T, Smit D, Jücker M, Menke A, Giehl K
CELL COMMUN SIGNAL. 2024;22(1):85.
2023
Activated Src kinases downstream of BCR-ABL and Flt3 induces proteasomal degradation of SHIP1 by phosphorylation of tyrosine 1021
Ehm P, Bettin B, Jücker M
BBA-MOL CELL RES. 2023;1870(5):.
Targeted hyperactivation of AKT through inhibition of ectopic expressed SHIP1 induces cell death in colon carcinoma cells and derived metastases
Ehm P, Linnebacher M, Block A, Rehbach C, Jücker M
CELL SIGNAL. 2023;108:110720.
Reduced expression and activity of patient-derived SHIP1 phosphatase domain mutants
Ehm P, Nelson N, Giehler S, Schaks M, Bettin B, Kirchmair J, Jücker M
CELL SIGNAL. 2023;101:.
SHIP1 Is Present but Strongly Downregulated in T-ALL, and after Restoration Suppresses Leukemia Growth in a T-ALL Xenotransplantation Mouse Model
Ehm P, Rietow R, Wegner W, Bußmann L, Kriegs M, Dierck K, Horn S, Streichert T, Horstmann M, Jücker M
CELLS-BASEL. 2023;12(13):1798.
Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo
Genduso S, Freytag V, Schetler D, Kirchner L, Schiecke A, Maar H, Wicklein D, Gebauer F, Bröker K, Stürken C, Milde-Langosch K, Oliveira-Ferrer L, Ricklefs F, Ewald F, Wolters-Eisfeld G, Riecken K, Unrau L, Krause L, Bohnenberger H, Offermann A, Perner S, Sebens S, Lamszus K, Diehl L, Linder S, Jücker M, Schumacher U, Lange T
J HEMATOL ONCOL. 2023;16(1):.
Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis
Kempska J, Oliveira-Ferrer L, Grottke A, Qi M, Alawi M, Meyer F, Borgmann K, Hamester F, Eylmann K, Rossberg M, Smit D, Jücker M, Laakmann E, Witzel I, Schmalfeldt B, Müller V, Legler K
FRONT ONCOL. 2023;13:1129682.
Generating Patient-Derived HCC Cell Lines Suitable for Predictive In Vitro and In Vivo Drug Screening by Orthotopic Transplantation
Staffeldt L, Mattert G, Riecken K, Rövenstrunk G, Volkmar A, Heumann A, Moustafa M, Jücker M, Fehse B, Schumacher U, Lüth S, Kah J
CELLS-BASEL. 2023;13(1):.
The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism
Tian L, Smit D, Jücker M
INT J MOL SCI. 2023;24(3):.
2022
Investigation of the function of the PI3-Kinase / AKT signaling pathway for leukemogenesis and therapy of acute childhood lymphoblastic leukemia (ALL)
Ehm P, Grottke A, Bettin B, Jücker M
CELL SIGNAL. 2022;93:.
Activation of CD44/PAK1/AKT signaling promotes resistance to FGFR1 inhibition in squamous-cell lung cancer
Elakad O, Häupl B, Labitzky V, Yao S, Küffer S, von Hammerstein-Equord A, Danner B, Jücker M, Urlaub H, Lange T, Ströbel P, Oellerich T, Bohnenberger H
NPJ PRECIS ONCOL. 2022;6(1):.
JAK2-V617F is a negative regulation factor of SHIP1 protein and thus influences the AKT signaling pathway in patients with Myeloproliferative Neoplasm (MPN)
Glück M, Dally L, Jücker M, Ehm P
INT J BIOCHEM CELL B. 2022;149:.
Combined Targeting of AKT and mTOR Inhibits Tumor Formation of EpCAM+ and CD90+ Human Hepatocellular Carcinoma Cells in an Orthotopic Mouse Model
Moustafa M, Dähling K, Günther A, Riebandt L, Smit D, Riecken K, Schröder C, Zhuang R, Krech T, Kriegs M, Fehse B, Izbicki J, Fischer L, Nashan B, Li J, Jücker M
CANCERS. 2022;14(8):.
The Functional Role of Extracellular Matrix Proteins in Cancer
Popova N, Jücker M
CANCERS. 2022;14(1):.
AKT Isoforms as a Target in Cancer and Immunotherapy
Smit D, Jücker M
2022. PI3K and AKT Isoforms in Immunity. Dominguez-Villar M (eds.). 1. ed. Cham: Springer, 409-436.
2021
Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia
Ecker V, Stumpf M, Brandmeier L, Neumayer T, Pfeuffer L, Engleitner T, Ringshausen I, Nelson N, Jücker M, Wanninger S, Zenz T, Wendtner C, Manske K, Steiger K, Rad R, Müschen M, Ruland J, Buchner M
NAT COMMUN. 2021;12(1):3526.
Knockdown of AKT3 Activates HER2 and DDR Kinases in Bone-Seeking Breast Cancer Cells, Promotes Metastasis In Vivo and Attenuates the TGFβ/CTGF Axis
Hinz N, Baranowsky A, Horn M, Kriegs M, Sibbertsen F, Smit D, Clezardin P, Lange T, Schinke T, Jücker M
CELLS-BASEL. 2021;10(2):.
AKT in Bone Metastasis of Solid Tumors: A Comprehensive Review
Hinz N, Jücker M
CANCERS. 2021;13(10):2287.
Truncated O-GalNAc glycans impact on fundamental signaling pathways in pancreatic cancer
Hofmann B, Picksak A, Kwiatkowski M, Grupp K, Jücker M, Bachmann K, Mercanoglu B, Izbicki J, Kahlert C, Bockhorn M, Güngör C, Ewald F, Wolters-Eisfeld G
GLYCOBIOLOGY. 2021;2021:.
AKT1 and PTEN show the highest affinities among phosphoinositide binding proteins for the second messengers PtdIns(3,4,5)P3 and PtdIns(3,4)P2
Nelson N, Razeto A, Gilardi A, Grättinger M, Kirchmair J, Jücker M
BIOCHEM BIOPH RES CO. 2021;568:110-115.
Combined Targeting of AKT and mTOR Synergistically Inhibits Formation of Primary Colorectal Carcinoma Tumouroids In Vitro: A 3D Tumour Model for Pre-therapeutic Drug Screening
Nörz D, Mullins C, Smit D, Linnebacher M, Hagel G, Mirdogan A, Siekiera J, Ehm P, Izbicki J, Block A, Thastrup O, Jücker M
ANTICANCER RES. 2021;41(5):2257-2275.
The Role of mTOR Signaling as a Therapeutic Target in Cancer
Popova N, Jücker M
INT J MOL SCI. 2021;22(4):1743.
Circulating tumor cells as a promising target for individualized drug susceptibility tests in cancer therapy
Smit D, Pantel K, Jücker M
BIOCHEM PHARMACOL. 2021;188:114589.
2020
Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity
Koch C, Kuske A, Joosse S, Yigit G, Sflomos G, Thaler S, Smit D, Werner S, Borgmann K, Gärtner S, Mossahebi Mohammadi P, Battista L, Cayrefourcq L, Altmüller J, Salinas-Riester G, Raithatha K, Zibat A, Goy Y, Ott L, Bartkowiak K, Tan T, Zhou Q, Speicher M, Müller V, Gorges T, Jücker M, Thiery J, Brisken C, Riethdorf S, Alix-Panabières C, Pantel K
EMBO MOL MED. 2020;12(9):.
Modeling Spontaneous Bone Metastasis Formation of Solid Human Tumor Xenografts in Mice
Labitzky V, Baranowsky A, Maar H, Hanika S, Starzonek S, Ahlers A, Stübke K, Koziolek E, Heine M, Schäfer P, Windhorst S, Jücker M, Riecken K, Amling M, Schinke T, Schumacher U, Valentiner U, Lange T
CANCERS. 2020;12(2):.
PI3K/AKT/mTOR signaling as a molecular target in head and neck cancer
Marquard F, Jücker M
BIOCHEM PHARMACOL. 2020;172:113729.
Characterization of the substrate specificity of the inositol 5-phosphatase SHIP1
Nelson N, Wundenberg T, Lin H, Rehbach C, Horn S, Windhorst S, Jücker M
BIOCHEM BIOPH RES CO. 2020;524(2):366-370.
Ectopic Expression of Hematopoietic SHIP1 in Human Colorectal Cancer
Schaks M, Allgoewer K, Nelson N, Ehm P, Heumann A, Ewald F, Schumacher U, Simon R, Sauter G, Jücker M
BIOMEDICINES. 2020;8(7):.
Combined Targeting of AKT and mTOR Inhibits Proliferation of Human NF1-Associated Malignant Peripheral Nerve Sheath Tumour Cells In Vitro but not in a Xenograft Mouse Model In Vivo
Schulte A, Ewald F, Spyra M, Smit D, Jiang W, Salamon J, Jücker M, Mautner V
INT J MOL SCI. 2020;21(4):.
High Sensitivity of Circulating Tumor Cells Derived from a Colorectal Cancer Patient for Dual Inhibition with AKT and mTOR Inhibitors
Smit D, Cayrefourcq L, Haider M, Hinz N, Pantel K, Alix-Panabières C, Jücker M
CELLS-BASEL. 2020;9(9):.
Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer
Voß H, Wurlitzer M, Smit D, Ewald F, Alawi M, Spohn M, Indenbirken D, Omidi M, David K, Juhl H, Simon R, Sauter G, Fischer L, Izbicki J, Molloy M, Nashan B, Schlüter H, Jücker M
CLIN EXP METASTAS. 2020;37(6):649-656.
2019
Analysis of the FLVR motif of SHIP1 and its importance for the protein stability of SH2 containing signaling proteins
Ehm P, Lange F, Hentschel C, Jepsen A, Glück M, Nelson N, Bettin B, de Bruyn Kops C, Kirchmair J, Nalaskowski M, Jücker M
CELL SIGNAL. 2019;63:109380.
Distinct functions of AKT isoforms in breast cancer: a comprehensive review
Hinz N, Jücker M
CELL COMMUN SIGNAL. 2019;17(1):154.
2018
Nuclear accumulation of SHIP1 mutants derived from AML patients leads to increased proliferation of leukemic cells
Nalaskowski M, Ehm P, Rehbach C, Nelson N, Täger M, Modest K, Jücker M
CELL SIGNAL. 2018;49:87-94.
2017
PTEN mediates the cross talk between breast and glial cells in brain metastases leading to rapid disease progression
Hohensee I, Chuang H, Grottke A, Werner S, Schulte A, Horn S, Lamszus K, Bartkowiak K, Witzel I, Westphal M, Matschke J, Glatzel M, Jücker M, Pukrop T, Pantel K, Wikman H
ONCOTARGET. 2017;8(4):6155-6168.
Combined inhibition of GLI and FLT3 signaling leads to effective anti-leukemic effects in human acute myeloid leukemia
Latuske E, Stamm H, Klokow M, Vohwinkel G, Muschhammer J, Bokemeyer C, Jücker M, Kebenko M, Fiedler W, Wellbrock J
ONCOTARGET. 2017;8(17):29187-29201.
SHIP1, but not an AML-derived SHIP1 mutant, suppresses myeloid leukemia growth in a xenotransplantation mouse model
Täger M, Horn S, Latuske E, Ehm P, Schaks M, Nalaskowski M, Fehse B, Fiedler W, Stocking C, Wellbrock J, Jücker M
GENE THER. 2017;24(11):749-753.
Akt1 and Akt3 but not Akt2 through interaction with DNA-PKcs stimulate proliferation and post-irradiation cell survival of K-RAS-mutated cancer cells
Toulany M, Maier J, Iida M, Rebholz S, Holler M, Grottke A, Jüker M, Wheeler D, Rothbauer U, Rodemann H
CELL DEATH DISCOV. 2017;(3):17072.
Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing
Volksdorf T, Heilmann J, Eming S, Schawjinski K, Zorn-Kruppa M, Ueck C, Vidal-Y-Sy S, Windhorst S, Jücker M, Moll I, Brandner J
AM J PATHOL. 2017;187(6):1301-1312.
2016
Downregulation of AKT3 Increases Migration and Metastasis in Triple Negative Breast Cancer Cells by Upregulating S100A4
Grottke A, Ewald F, Lange T, Nörz D, Herzberger C, Bach J, Grabinski N, Gräser L, Höppner F, Nashan B, Schumacher U, Jücker M
PLOS ONE. 2016;11(1):e0146370.
Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells
Holler M, Grottke A, Mueck K, Manes J, Jücker M, Rodemann H, Toulany M
PLOS ONE. 2016;11(5):e0154745.
Akt isoform specific effects in ovarian cancer progression
Linnerth-Petrik N, Santry L, Moorehead R, Jücker M, Wootton S, Petrik J
ONCOTARGET. 2016;7(46):74820-74833.
2015
The tumor suppressor SHIP1 colocalizes in nucleolar cavities with p53 and components of PML nuclear bodies
Ehm P, Nalaskowski M, Wundenberg T, Jücker M
NUCLEUS-PHILA. 2015;6(2):154-64.
Vertical Targeting of AKT and mTOR as Well as Dual Targeting of AKT and MEK Signaling Is Synergistic in Hepatocellular Carcinoma
Ewald F, Nörz D, Grottke A, Bach J, Herzberger C, Hofmann B, Nashan B, Jücker M
J CANCER. 2015;6(12):1195-205.
COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer
Hofmann B, Schlüter L, Lange P, Mercanoglu B, Ewald F, Fölster A, Picksak A, Harder S, El Gammal A, Grupp K, Güngör C, Drenckhan A, Schlüter H, Wagener C, Izbicki J, Jücker M, Bockhorn M, Wolters-Eisfeld G
MOL CANCER. 2015;14(1):109.
ErbB2 signaling activates the Hedgehog pathway via PI3K-Akt in human esophageal adenocarcinoma: Identification of novel targets for concerted therapy concepts
Kebenko M, Drenckhan A, Gros S, Jücker M, Grabinski N, Ewald F, Grottke A, Schultze A, Izbicki J, Bokemeyer C, Wellbrock J, Fiedler W
CELL SIGNAL. 2015;27(2):373-81.
Discontinuing MEK inhibitors in tumor cells with an acquired resistance increases migration and invasion
Nörz D, Grottke A, Bach J, Herzberger C, Hofmann B, Nashan B, Jücker M, Ewald F
CELL SIGNAL. 2015;27(11):2191-200.
Expression of Hedgehog Pathway Mediator GLI Represents a Negative Prognostic Marker in Human Acute Myeloid Leukemia and Its Inhibition Exerts Antileukemic Effects
Wellbrock J, Latuske E, Köhler J, Wagner K, Stamm H, Vettorazzi E, Vohwinkel G, Klokow M, Uibeleisen R, Ehm P, Riecken K, Loges S, Thol F, Schubert C, Amling M, Jücker M, Bokemeyer C, Heuser M, Krauter J, Fiedler W
CLIN CANCER RES. 2015.
Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic acid induced 2
Werner S, Brors B, Eick J, Marques E, Pogenberg V, Parret A, Kemming D, Wood A, Edgren H, Neubauer H, Streichert T, Riethdorf S, Bedi U, Baccelli I, Jücker M, Eils R, Fehm T, Trumpp A, Johnsen S, Klefstrom J, Wilmanns M, Müller V, Pantel K, Wikman-Kocher H
CANCER DISCOV. 2015;5(5):506-19.
2014
"Alkohol und Nikotin"-Konzept und Evaluation eines interdisziplinären Wahlfachs mit OSPE im Studienabschnitt Medizin 1
Bergelt C, Lauke-Wettwer H, Petersen-Ewert C, Jücker M, Bauer C
GMS J MED EDU. 2014;31(1):1-20.
H2S preconditioning of human adipose tissue-derived stem cells increases their efficacy in an in vitro model of cell therapy for simulated ischemia
Dongó E, Benkő Z, Csizmazia Á, Marosi G, Grottke A, Jücker M, Schumacher U, Kiss L
LIFE SCI. 2014;113(1-2):14-21.
Dual Inhibition of PI3K-AKT-mTOR- and RAF-MEK-ERK-signaling is synergistic in cholangiocarcinoma and reverses acquired resistance to MEK-inhibitors
Ewald F, Nörz D, Grottke A, Hofmann B, Nashan B, Jücker M
INVEST NEW DRUG. 2014;32(6):1144-54.
AKT3 regulates ErbB2, ErbB3 and estrogen receptor α expression and contributes to endocrine therapy resistance of ErbB2(+) breast tumor cells from Balb-neuT mice
Grabinski N, Möllmann K, Milde-Langosch K, Müller V, Schumacher U, Brandt B, Pantel K, Jücker M
CELL SIGNAL. 2014;26(5):1021-9.
2013
Combined targeting of AKT and mTOR using MK-2206 and RAD001 is synergistic in the treatment of cholangiocarcinoma
Ewald F, Grabinski N, Grottke A, Windhorst S, Nörz D, Carstensen L, Staufer K, Hofmann B, Diehl F, David K, Schumacher U, Nashan B, Jücker M
INT J CANCER. 2013;133(9):2065-76.
2012
Leukemia-associated mutations in SHIP1 inhibit its enzymatic activity, interaction with the GM-CSF receptor and Grb2, and its ability to inactivate PI3K/AKT signaling.
Brauer H, Strauss J, Wegner W, Müller-Tidow C, Horstmann M, Jücker M
CELL SIGNAL. 2012;24(11):2095-2101.
Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells.
Grabinski N, Ewald F, Hofmann B, Staufer K, Schumacher U, Nashan B, Jücker M
MOL CANCER. 2012;11:85.
Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain.
Hofmann B, Jücker M
CELL SIGNAL. 2012;24(10):1950-1954.
The inositol 5-phosphatase SHIP1 is a nucleo-cytoplasmic shuttling protein and enzymatically active in cell nuclei.
Nalaskowski M, Metzner A, Brehm M, Labiadh S, Brauer H, Grabinski N, Mayr G, Jücker M
CELL SIGNAL. 2012;24(3):621-628.
2011
Distinct functional roles of Akt isoforms for proliferation, survival, migration and EGF-mediated signalling in lung cancer derived disseminated tumor cells
Grabinski N, Bartkowiak K, Grupp K, Brandt B, Pantel K, Jücker M
CELL SIGNAL. 2011;23(12):1952-1960.
Posttranscriptional regulation of the p85α adapter subunit of phosphatidylinositol 3-kinase in human leukemia cells
Hofmann B, Hoxha E, Mohr E, Schulz K, Jücker M
LEUKEMIA LYMPHOMA. 2011;52(3):467-477.
2009
Reduced proliferation of CD34(+) cells from patients with acute myeloid leukemia after gene transfer of INPP5D.
Metzner A, Precht C, Fehse B, Fiedler W, Stocking C, Günther A, Mayr G, Jücker M
GENE THER. 2009;16(4):570-573.
2008
Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential to hematopoietic cells.
Horn S, Bergholz U, Jücker M, McCubrey J, Trümper L, Stocking C, Bäsecke J
ONCOGENE. 2008;27(29):4096-4106.
2007
Gene transfer of SHIP-1 inhibits proliferation of juvenile myelomonocytic leukemia cells carrying KRAS2 or PTPN11 mutations.
Metzner A, Horstmann M, Fehse B, Ortmeyer G, Niemeyer C, Stocking C, Mayr G, Jücker M
GENE THER. 2007;14(8):699-703.
2003
An increase in the expression and total activity of endogenous p60(c-Src) in several factor-independent mutants of a human GM-CSF-dependent leukemia cell line (TF-1)
Horn S, Meyer J, Stocking C, Ostertag W, Jücker M
ONCOGENE. 2003;22(46):7170-80.
2002
Hierarchy of stroma-derived factors in supporting growth of stroma-dependent hemopoietic cells membrane-bound SCF is sufficient to confer stroma competence to epithelial cells
Friel J, Itoh K, Bergholz U, Jücker M, Stocking C, Harrison P, Ostertag W
GROWTH FACTORS. 2002;20(1):35-51.
1996
Expression of the neural adhesion molecule L1 in the deafferented dentate gyrus
Jucker M, D'Amato F, Mondadori C, Mohajeri H, Magyar J, Bartsch U, Schachner M
NEUROSCIENCE. 1996;75(3):703-15.
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