Thorben Huth

Mimicking liver inflammation to identify essential genes in hepatocellular carcinoma: Towards a CRISPR screen based on IL-6/STAT3 signaling

A Krumme, Yves Matthess, Thorben Huth, E Eiteneuer et autres

Hepatocellular carcinoma (HCC), the predominant form of liver cancer, is a leading cause of cancer-related mortality worldwide. Inflammation is central to HCC progression, with the interleukin-6 (IL-6)/STAT3 signaling pathway being frequently hyperactivated. Loss of heterozygosity (LoH) on chromosome 8p (chr8p) is a …

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ROBO receptors function as tumor suppressors in cholangiocarcinoma

Aslihan Inal, Freya Baeumlisberger, Kira Guer, Raisatun-Nisa Sugiyanto et autres

Introduction Cholangiocarcinoma (CCA) is a rare but highly aggressive malignancy of the bile duct with inadequate therapy options and poor prognosis. Genetic alterations in ROBO receptors were identified exclusively in the invasive form of CCA (Goeppert et.al, 2022). ROBO receptors act as …

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Proteomic profiling reveals CEACAM6 function in driving gallbladder cancer aggressiveness through integrin receptor, PRKCD and AKT/ERK signaling

Raisatun Nisa Sugiyanto, Carmen Metzger, Aslihan Inal, Felicia Truckenmueller et autres

Gallbladder cancer (GBC) presents as an aggressive malignancy with poor patient outcome. Like other epithelial cancers, the mechanisms of GBC cancer progression remain vague and efforts in finding targeted therapies fall below expectations. This study combined proteomic analysis of formalin-fixed paraffin-embedded (FFPE) …

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Phosphatidylinositol 4-Kinase III Alpha Governs Cytoskeletal Organization for Invasiveness of Liver Cancer Cells

Cong Si Tran, Julia Kersten, Jingyi Yan, Marco Breinig et autres

BACKGROUND & AIMS: High expression of phosphatidylinositol 4-kinase III alpha (PI4KIIIα) correlates with poor survival rates in patients with hepatocellular carcinoma. In addition, hepatitis C virus (HCV) infections activate PI4KIIIα and contribute to hepatocellular carcinoma progression. We aimed at mechanistically understanding the …

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Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer

Thorben Huth, Emely C. Dreher, Steffen Lemke, Sarah Fritzsche et autres

Large-scale chromosomal aberrations are prevalent in human cancer, but their function remains poorly understood. We established chromosome-engineered hepatocellular carcinoma cell lines using CRISPR-Cas9 genome editing. A 33-mega-base pair region on chromosome 8p (chr8p) was heterozygously deleted, mimicking a frequently observed chromosomal deletion. …

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Chromosome engineering and CRISPR-Cas9 viability screening reveals increased metastatic capacity targetable by patient-specific synthetic lethality

Thorben Huth, Emely C. Dreher, Steffen Lemke, Sarah Fritzsche et autres

Analysis of SH2D4A promoter activity reveals positive regulation by inflammatory cytokines via transcription factor KLF4.

Johannes Schreck, Carolin Ploeger, Thorben Huth, Raisatun-Nisa Sugiyanto et autres

Hepatocellular carcinoma is typically preceded by chronic liver damage and inflammation. Cytokines associated with tumor initiation, invasion, and metastasis are often elevated in the tumor microenvironment. SH2D4A acts as a tumor suppressor in HCC, shows a reduced expression in tumor tissue and …

STAT1 and STAT3 Exhibit a Crosstalk and Are Associated with Increased Inflammation in Hepatocellular Carcinoma

Carolin Ploeger, Johannes Schreck, Thorben Huth, Angelika Fraas et autres

Liver cancers, which are mostly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are very aggressive tumors with poor prognosis. Therapeutic options with curative intent are largely limited to surgery and available systemic therapies show limited benefit. Signal transducer and activator of transcription 1 …

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Prohibitin, STAT3 and SH2D4A physically and functionally interact in tumor cell mitochondria

Carolin Ploeger, Thorben Huth, Raisatun Nisa Sugiyanto, Stefan Pusch et autres

Chromosome 8p is frequently deleted in various cancer entities and has been shown to correlate with poor patient survival. SH2D4A is located on chromosome 8p and prevents the nuclear translocation of the pro-tumorigenic transcription factor STAT3. Here, we investigated the interaction of …

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