Project description:The molecular hallmark of immunogenic cell death (ICD) features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Herein, measuring DAMPs from gemcitabine-induced dying cancer cells, via mass spectrometry (MS) proteomic profiling.
Project description:Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen and progesterone receptors, and the lack of HER2 amplification or overexpression. Chemoresistance is currently one of the major challenges in the treatment TNBC. Therefore, there is a need towards identification of the novel molecular targets that could be exploited to overcome TNBC chemoresistance. In this study, we found that knock-down of Mixed-Lineage Kinase 4 (MLK4), a member of MAP3K family of serine/threonine kinases, sensitizes TNBC cell to chemotherapy and impairs activation of DNA repair pathways upon genotoxic treatment. DNA damage response signaling network coordinates transcriptional response at multiple levels to preserve cellular homeostasis and promote survival in response to genotoxic stress. Since MLK4-deficient cells were compromised for DNA damage response signaling activation following doxorubicin treatment, we hypothesized that the loss of MLK4 could significantly affect global transcriptomic changes induced by chemotherapy in TNBC cells. To test this hypothesis we performed gene expression profiling by mRNA-seq in HCC1806 TNBC cells transfected with control or MLK4-targeting siRNAs and treated with either 1 μM of doxorubicin for 24 h or vehicle only (DMSO control). Our RNA-seq analysis revealed that MLK4 is required for DNA damage-induced expression of several NF-кB-associated cytokines, including IL-6, which facilitates TNBC cells survival in an autocrine manner.
Project description:The molecular hallmark of immunogenic cell death (ICD) features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Herein, measuring DAMPs from gemcitabine-induced dying cancer cells, via mass spectrometry (MS) proteomic profiling.
Project description:We propose to definitively characterise the somatic genetics of triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.
Project description:The aim of this study was evaluate the transcriptome changes in the comparison between triple negative tumors with increased SPARC expression and triple negative tumors with decreased SPARC expression according to Nagai et al., 2011 (Breast Cancer Res Treat (2011) 126:1–14) The results generated could be of particular interest to better define the prognostic impact of SPARC expression in triple negative breast tumors
Project description:Triple negative breast cancer (TNBC) represents a challenging tumor type due to their poor prognosis and limited treatment options. It is well recognize that clinical and molecular heterogeneity of TNBC is driven in part by mRNA and lncRNAs. To stratify TNBCs, we profiled mRNAs and lncRNA in 158 adjuvant TNBC tumors using an Affymetrix microarray platform. Lehmann clustering analysis allowed us to identify TNBC subtypes featuring unique lncRNA expression patterns, disease free and overall survival rates and particular gene ontology enrichments (performed with GSEA algorithm).
Project description:Triple negative breast cancer (TNBC) represents a challenging tumor type due to their poor prognosis and limited treatment options. It is well recognize that clinical and molecular heterogeneity of TNBC is driven in part by mRNA and lncRNAs. To stratify TNBCs, we profiled mRNAs and lncRNA in 158 adjuvant TNBC tumors using an Affymetrix microarray platform. Lehmann clustering analysis allowed us to identify TNBC subtypes featuring unique lncRNA expression patterns, disease free and overall survival rates and particular gene ontology enrichments (performed with GSEA algorithm).