Project description:An shRNA screen with the aim to investigate the role of pancreatic cancer-associated genes in the metastatic outgrowth in vivo was carried out. The set of candidate genes (284) was selected based on their association with pancreatic cancer, frequency of mutation in pancreatic cancer or on being Ras-regulated.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Currently, there is no effective therapy to treat PDAC, and thus detailed molecular and functional evaluation of PDAC is needed to identify and develop better therapeutic strategies. Here we show that the transcription factor Kruppel-like factor 7 (KLF7) is overexpressed in PDAC and that inhibition of KLF7 blocks PDAC tumor growth and metastasis in cell culture and in mice. KLF7 expression in PDAC can be upregulated due to activation of a MAP kinase pathway or inactivation of the tumor suppressor p53, two alterations that occur in a large majority of PDACs. ShRNA-mediated knockdown of KLF7 inhibits the expression of interferon-stimulated genes (ISGs), which are necessary for KLF7-mediated PDAC tumor growth and metastasis. KLF7 knockdown also results in the downregulation of Discs Large MAGUK Scaffold Protein 3 (DLG3), resulting in Golgi complex fragmentation, and reduced protein glycosylation leading to reduced secretion of cancer-promoting growth factors such as chemokines. Genetic or pharmacological activation of Golgi complex fragmentation blocks PDAC growth and metastasis similar to KLF7 inhibition. Our results demonstrate a therapeutically amenable, KLF7-driven pathway that promotes PDAC growth and metastasis by activating ISGs and maintaining Golgi complex integrity.
Project description:We used single cell RNA sequencing to investigate macrophage heterogeneity and their temporal and spatial distributions in PDAC liver metastasis
Project description:Aberrant expression of truncated O-glycan structures, such as Tn and STn, is frequently observed in pancreatic ductal adenocarcinoma (PDAC). The focus of our study is to investigate the functional role of truncated O-glycans in PDAC progression and metastasis. Our study revealed that kmockout of C1GALT1 leads to increased expression of truncated glycans and accelerates PDAC progression and metastasis.
Project description:We used single cell RNA sequencing to investigate how macrophages regulate tumor-associated fibroblast heterogeneity in PDAC liver metastasis
Project description:The uploaded data are described within "Screen Identifies DYRK1B Network as Mediator of Transcription Repression on Damaged Chromatin". In short, peptides from RPE1 epithelial cells with either normal expression of DYRK1B, over expression, of knockout of the kinase were TMT11 plex labeled and enriched by tandem phosphopeptide enrichment.