Genome‐wide cooperation of
            <scp>EMT</scp>
            transcription factor
            <scp>ZEB</scp>
            1 with
            <scp>YAP</scp>
            and
            <scp>AP</scp>
            ‐1 in breast cancer

Feldker, Nora; Ferrazzi, Fulvia; Schuhwerk, Harald; Widholz, Sebastian A.; Guenther, Kerstin; Frisch, Isabell; Jakob, Kathrin; Kleemann, Julia; Riegel, Dania; Bönisch, Ulrike; Lukassen, Soeren; Eccles, Rebecca L; Schmidl, Christian; Stemmler, Marc P.; Brabletz, Thomas; Brabletz, Simone

doi:10.15252/embj.2019103209

Cited by 119 publications

(89 citation statements)

References 85 publications

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“…The classical EMT-TFs include the zinc-finger E-box binding homeobox factors ZEB1 and ZEB2, Snail (SNAI1), SLUG (SNAI2), and the basic helix-loop-helix factors TWIST1 and TWIST2 [ 99 ]. However, other transcription factors have been identified to be critical in the progression of EMT in different tumors [ 100 , 101 ]. A feature which strengthens the robustness of the EMT once initiated is the positive feedback among EMT-TFs.…”

Section: Src Family Kinases In the Epithelial Mesenchymal Transition (Emt)mentioning

confidence: 99%

Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition

Ortiz

Mikhailova

et al. 2021

Cell Commun Signal

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Over a century of scientific inquiry since the discovery of v-SRC but still no final judgement on SRC function. However, a significant body of work has defined Src family kinases as key players in tumor progression, invasion and metastasis in human cancer. With the ever-growing evidence supporting the role of epithelial-mesenchymal transition (EMT) in invasion and metastasis, so does our understanding of the role SFKs play in mediating these processes. Here we describe some key mechanisms through which Src family kinases play critical role in epithelial homeostasis and how their function is essential for the propagation of invasive signals.

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Section: Src Family Kinases In the Epithelial Mesenchymal Transition (Emt)mentioning

confidence: 99%

Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition

Ortiz

Mikhailova

et al. 2021

Cell Commun Signal

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“…ACE2 are not only expressed in both upper and lower respiratory tract but also in cell of small intestine, pancreas, kidneys, heart, oesophagus, bladder and brain making them all vulnerable to infection by SARS-CoV-2 [ 11 ]. It is noteworthy that normal ACE2 expression is not very high in upper respiratory tract and is only transiently enhanced in response to infection with SARS-CoV-2 for increased transmissibility of the virus [ 12 ]. Also, ACE2 expression in other tissues explains the development of multi-organ failure that often accompanies severe COVID-19 infection [ 13 , 14 ].…”

Section: Covid-19 Pathogenesismentioning

confidence: 99%

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm

et al. 2021

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COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

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“…To further investigate the role of the CD70 signaling network in GBM, we investigated transcriptional changes and their predicted networks after CD70 silencing using RNA sequencing and subsequent gene set enrichment analysis (GSEA). Using three GBM lines transduced with shCD70 or shGFP, we observed strong downregulation of FOSL1, a gene recently discovered to play a pivotal role in stemness, migration, and EMT (SupplFig3A) (Fiscon, Conte, and Paci, 2018;Feldker et al 2020). Other slightly downregulated genes included CDH2 (Cadherin 2), PLAUR, and CXCR4; genes known to be associated with the Mesenchymal subtype in GBM and a worse overall prognosis (Gilder et al 2018;Tao et al 2020;Yi et al 2018).…”

Section: Cd70 Plays a Crucial Role In Cellular Programs Implicated In Tumorigenesismentioning

confidence: 88%

Hitting more birds with one stone: CD70 as an actionable immunotherapeutic target in recurrent glioblastoma

Seyfrid

Maich

et al. 2021

Preprint

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Purpose: Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of brain tumor initiating cells (BTICs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here we identify CD70 as a potential therapeutic target for recurrent GBM BTICs. Experimental Design: In the current study, we identified the relevance and functional influence of CD70 on primary and recurrent GBM cells, and further define its function using established stem cell assays. We utilize CD70 knockdown studies, subsequent RNAseq pathway analysis, and in vivo xenotransplantation to validate the role of CD70 in GBM. Next, we developed and tested an anti-CD70 CAR-T therapy, which we validated in vitro and in vivo using our established preclinical model of human GBM. Lastly, we explored the importance of CD70 in the tumor immune microenvironment (TIME) by assessing the presence of its receptor, CD27, in immune infiltrates derived from freshly resected GBM tumor samples. Results: CD70 expression is elevated in recurrent GBM and CD70 knockdown reduces tumorigenicity in vitro and in vivo. CD70 CAR-T therapy significantly improves prognosis in vivo. We also found CD27 to be present on the cell surface of multiple relevant GBM TIME cell populations. Conclusion: CD70 plays a key role in recurrent GBM cell aggressiveness and maintenance. Immunotherapeutic targeting of CD70 significantly improves survival in animal models and the CD70/CD27 axis may be a viable poly-therapeutic avenue to co-target both GBM and its TIME.

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Genome‐wide cooperation of EMT transcription factor ZEB 1 with YAP and AP ‐1 in breast cancer

Cited by 119 publications

References 85 publications

Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition

Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm

Hitting more birds with one stone: CD70 as an actionable immunotherapeutic target in recurrent glioblastoma

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