Journal: Cancer Letters

Abbreviation

Cancer Lett

Publisher

Elsevier

Journal Volumes

ISSN

0304-3835
1872-7980

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Publications 1 - 5 of 5
  • Myotubularin-related-protein-7 inhibits mutant (G12V) K-RAS by direct interaction
    Item type: Journal Article
    Weidner, Philip; Saar, Daniel; Söhn, Michaela; et al. (2024)
    Cancer Letters
    Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers.
  • High affinity and covalent-binding microtubule stabilizing agents show activity in chemotherapy-resistant acute myeloid leukemia cells
    Item type: Journal Article
    Pera, Benet; Calvo-Vidal, M. Nieves; Ambati, Srikanth; et al. (2015)
    Cancer Letters
  • Teneurin protein family
    Item type: Review Article
    Ziegler, Annemarie; Corvalan, Alejandro; Roa, Iván; et al. (2012)
    Cancer Letters
  • Antibodies Directed Against L1-CAM Synergize with Genistein in Inhibition Growth and Survival Pathways in SKOV3ip Human Ovarian Cancer Cells
    Item type: Journal Article
    Novak-Hofer, Ilse; Cohrs, Susan; Grünberg, Jürgen; et al. (2008)
    Cancer Letters
  • Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development
    Item type: Journal Article
    Sun, Suna; Frontini, Francesca; Qi, Weihong; et al. (2021)
    Cancer Letters
    Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV (“MesoERV1-12”) were identified and verified by qPCR in mouse tissues. “MesoERV1-12” expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. “MesoERV1-12” levels were significantly increased by demethylating agent 5-Aza-2′-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. “MesoERV7” promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.
Publications 1 - 5 of 5