TY  - JOUR
A1  - Leikam, C
A1  - Hufnagel, AL
A1  - Otto, C
A1  - Murphy, DJ
A1  - Mühling, B
A1  - Kneitz, S
A1  - Nanda, I
A1  - Schmid, M
A1  - Wagner, TU
A1  - Haferkamp, S
A1  - Bröcker, E-B
A1  - Schartl, M
A1  - Meierjohann, S
T1  - In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells
JF  - Cell Death and Disease
N2  - Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi-or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS\(^{61K}\) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.
KW  - reactive oxygen
KW  - human melanoma
KW  - MITF
KW  - cancer
KW  - skin
KW  - DNA damage
KW  - kappa-B
KW  - oncogene-induced senescence
KW  - cellular senescence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148718
VL  - 6
IS  - e1711
ER  - 
TY  - JOUR
A1  - Herweg, Jo-Ana
A1  - Hansmeier, Nicole
A1  - Otto, Andreas
A1  - Geffken, Anna C.
A1  - Subbarayal, Prema
A1  - Prusty, Bhupesh K.
A1  - Becher, Dörte
A1  - Hensel, Michael
A1  - Schaible, Ulrich E.
A1  - Rudel, Thomas
A1  - Hilbi, Hubert
T1  - Purification and proteomics of pathogen-modified vacuoles and membranes
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.
KW  - spectrometry-based proteomics
KW  - Mycobacterium tuberculosis
KW  - Chlamydia
KW  - Salmonella
KW  - bacterium Legionella pneumophila
KW  - endocytic multivesicular bodies
KW  - phagosome maturation arrest
KW  - III secretion system
KW  - endoplasmic reticulum
KW  - Chlamydia trachomatis
KW  - Simkania negevensis
KW  - intracellular bacteria
KW  - host pathogen interactions
KW  - immuno-magnetic purification
KW  - Legionella
KW  - Mycobacterium
KW  - Simkania
KW  - pathogen vacuole
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151823
VL  - 5
IS  - 48
ER  -