Project description:ATP-competitive p97 inhibitor CB-5339, the successor of CB-5083, is being evaluated in Phase 1 clinical trials for anti-cancer therapy. Different modes of action p97 inhibitors such as allosteric inhibitors are useful to overcome one the major problems of targeted therapy: drug-induced resistance. We previously demonstrated allosteric p97 inhibitor NMS-873 can overcome CB-5083-induced resistance. Here, we found that NMS-873 but not CB-5083 affected glycometabolism. By establishing NMS-873-resistant cell lines and performing both cell-based and proteomic analysis, we confirmed that NMS-873 dysregulates glycometabolism in a p97-independent manner. We then used proteome integral solubility alteration with a temperature-based method (PISA T) to identify NDUFAF5 as one of the potential targets of NMS-873 in the mitochondrial complex I. Overall, we employed chemical proteomics and drug-induced thermal proteome changes to identify drug targets, in combination with drug-resistant cell lines to dissect on- and off-target effects. We also demonstrated that glycolysis inhibitor 2-DG enhanced the anti-proliferative effect of NMS-873. The polypharmacology of NMS-873 can be advantageous for anti-cancer therapy.
Project description:We used expression profiling of colorectal cancer and endometrial cancer cell lines treated with demethylating agents to search for epigenetically regulated miRNAs. The study included three MMR-deficient colorectal cancer cell lines (HCT116, HCT15, and RKO), two MMR-proficient colorectal cancer cell lines (SW480, and T84) and two MMR-deficient endometrial cancer cell lines (AN3CA and HEC59).
Project description:Using H3K27ac ChIP-seq profile to map active enhancers in lung cancer and endometrial carcinoma cells ChIP-seq of H3K27ac was done in lung adenocarcinoma cell lines (NCI-H358 and NCI-H2009), squamous cell lung carcinoma cell lines (HCC95) and endometrial carcinoma cell lines (Ishikawa)
Project description:Cancer stem cells (CSCs) are crucial for tumor initiation, growth, dissemination, and resistance to therapy. In this study, we aimed to evaluate the effect of inhibiting aldehyde dehydrogenase (ALDH), an enzyme present in endometrial CSCs, using N,N-diethylaminobenzaldehyde (DEAB). This study aimed to evaluate the effects of ALDH inhibition in endometrial cancer stem cells (CSCs). ECC-1 and RL95-2 cell lines were subjected to proteome profiling with and without N,N-diethylaminobenzaldehyde (DEAB).
Project description:Cell body and pseudopod RNA are differentially regulated during the migration of the metastatic cancer cells.We wanted to identify the RNA which are upregulated in the pseudopodial (PS) fraction as compared to cell body fraction (CB). We used microarray to see which are the RNAs upregulated in the PS fraction as compared to CB fraction PS and CB fractions were isolated from six different metatstatic cell lines
Project description:AZD4547,pan-FGFR inhibitor, have been reported to have profound therapeutic effects on FGFR-deregulated cancers. AN3-CA is one of endometrial cancer cell lines harbouring FGFR2 mutants. AZD4547 showed a potent antiprolierative effect on AN3-CA cells. we used microarray to investigate transcriptome-wide change in gene expression followinig 300 nM AZD4547 treatment to explain the chemotherapeutic effect. compound treatment with or without ligand stimulus.
Project description:AZD4547,pan-FGFR inhibitor, have been reported to have profound therapeutic effects on FGFR-deregulated cancers. AN3-CA is one of endometrial cancer cell lines harbouring FGFR2 mutants. AZD4547 showed a potent antiprolierative effect on AN3-CA cells. we used microarray to investigate transcriptome-wide change in gene expression followinig 300 nM AZD4547 treatment to explain the chemotherapeutic effect.
