Project description:Cancer cells function as primary architects of the tumor microenvironment. Yet, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis.
Project description:Cancer cells function as primary architects of the tumor microenvironment. Yet, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis.
Project description:Compare the difference between pairwise aNOF and CAF samples for two patients patient #225: aNOF #225 vs CAF #225 patient #248: aNOF #248 vs CAF #248
Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls. comparison 1: CAF co-cultured with OSCC vs. mono-cultured CAF comparison 2: OSCC co-cultured with CAF vs. mono-cultured OSCC 1.7X10(5) YD-10B OSCC cells and 1.7X10(5) CAF were seeded in the upper chamber and lower chamber, respectively, of 6-transwell plates containing collagen-coated 1 micrometer pore transmembrane filters (Becton Dickinson, Franklin Lakes, NJ, USA). Monoculture control samples were generated by culturing only CAF or OSCC on the same side of the filter as in the co-culture design.
Project description:Chromatin assembly factor CAF-1 is conserved in all eukaryotes. In contrast to animals, plant CAF-1 is viable. Here we probe effects of loss of CAF-1 on the transcriptome of non-diving cells. Fully expanded rosette leaf 6 was collected from 10 35-d-old plants grown in short day photoperiods of wild type Col and CAF-1 mutants fas2-4 were used for RNA extraction.
Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls.
Project description:Chromatin assembly factor CAF-1 is conserved in all eukaryotes. In contrast to animals, plant CAF-1 is viable. Here we probe effects of loss of CAF-1 on the transcriptome of non-diving cells. Fully expanded rosette leaf 6 was collected from 10 35-d-old plants grown in short day photoperiods of wild type Col and CAF-1 mutants fas2-4 generation 1 and generation 6 were used for RNA extraction.