Anna‐Lena Scherr

Lymphotoxin beta‐activated LTBR/NIK/RELB axis drives proliferation in cholangiocarcinoma

Kaiyu Xu, Annika Kessler, Federico Nichetti, Paula Hoffmeister‐Wittmann et autres

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the intrahepatic (iCCA) or extrahepatic (eCCA) bile ducts with poor prognosis and limited treatment options. Prior evidence highlighted a significant contribution of the non-canonical NF-κB signalling pathway in initiation and aggressiveness …

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Etiology-independent activation of the LTβ-LTβR-RELB axis drives aggressiveness and predicts poor prognosis in HCC

Anna‐Lena Scherr, Luisa Nader, Kaiyu Xu, Christin Elßner et autres

BACKGROUND AND AIMS: HCC is the most common primary liver tumor, with an increasing incidence worldwide. HCC is a heterogeneous malignancy and usually develops in a chronically injured liver. The NF-κB signaling network consists of a canonical and a noncanonical branch. Activation …

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Bcl‐xL as prognostic marker and potential therapeutic target in cholangiocarcinoma

Paula Hoffmeister‐Wittmann, Andreas Möck, Federico Nichetti, Felix Korell et autres

Abstract Intrahepatic, perihilar, and distal cholangiocarcinoma (iCCA, pCCA, dCCA) are highly malignant tumours with increasing mortality rates due to therapy resistances. Among the mechanisms mediating resistance, overexpression of anti‐apoptotic Bcl‐2 proteins (Bcl‐2, Bcl‐xL, Mcl‐1) is particularly important. In this study, we investigated …

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Specific Targeting of Antiapoptotic Bcl-2 Proteins as a Radiosensitizing Approach in Solid Tumors

Benjamin Sobol, Osama Azzam Nieto, Emily Lara Eberlein, Anna‐Lena Scherr et autres

Avoidance of therapy-induced apoptosis is a hallmark of acquired resistance towards radiotherapy. Thus, breaking resistance still challenges modern cancer therapy. The Bcl-2 protein family is known for its regulatory role in apoptosis signaling, making Bcl-2, Mcl-1 and Bcl-xL promising targets. This study …

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RELB activation drives tumour aggressiveness and predicts prognosis in hepatocellular carcinoma

Luisa Nader, Federico Nichetti, Anna‐Lena Scherr, Christin Elßner et autres

Caspase‐8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice

Nathalie Tisch, Carolin Mogler, Ana Stojanovic, Robert Luck et autres

The gut has a specific vascular barrier that controls trafficking of antigens and microbiota into the bloodstream. However, the molecular mechanisms regulating the maintenance of this vascular barrier remain elusive. Here, we identified Caspase-8 as a pro-survival factor in mature intestinal endothelial …

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Non-canonical NF-κB signaling induces proliferation in primary liver cancer

AnnikaSophia Keßler, Luisa Nader, Anna‐Lena Scherr, Nathalie Schmitt et autres

Background and Aims Primary liver cancer is the third leading cause of cancer related death with increasing incidence and mortality worldwide. Recent studies demonstrate a role of non-canonical nuclear factor kappa B (NF-κB) signaling in various chronic liver diseases. Here, we aimed …

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Identification of BCL-XL as highly active survival factor and promising therapeutic target in colorectal cancer

Anna‐Lena Scherr, Andreas Möck, Georg Gdynia, Nathalie Schmitt et autres

Since metastatic colorectal cancer (CRC) is a leading cause of cancer-related death, therapeutic approaches overcoming primary and acquired therapy resistance are an urgent medical need. In this study, the efficacy and toxicity of high-affinity inhibitors targeting antiapoptotic BCL-2 proteins (BCL-2, BCL-XL, and …

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MCL1 Is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice

Marc E. Healy, Yannick Boege, Michael C. Hodder, Friederike Böhm et autres

Background & Aims Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 …

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Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells

Anna‐Lena Scherr, Adam Jassowicz, Anna Pató, Christin Elßner et autres

Autophagy is a catabolic process that enables cells to degrade obsolete content and refuel energy depots. In colorectal cancer (CRC) autophagy has been shown to promote tumorigenesis through energy delivery in the condition of uncontrolled proliferation. With this study, we aimed at …

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Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice

Christin Elßner, Benjamin Goeppert, Thomas Longerich, Anna‐Lena Scherr et autres

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The role of anti-apoptotic Bcl-2 proteins for colorectal cancer development and progression

Anna‐Lena Scherr

Anti-apoptotic Bcl-2 (B-cell lymphoma 2) proteins such as Bcl-2 itself, Bcl-xL and Mcl-1, prevent mitochondrial activation and thereby the induction of the intrinsic apoptotic signaling pathway. Since the avoidance of cell death is a prerequisite for malignant transformation, anti-apoptotic proteins are frequently …