The mechanisms that allow breast cancer cells to metabolically sustain growth are poorly understood. In breast cancer, FoxA1 transcription factor, along with estrogen receptor, regulates luminal cell specification and proliferation. Here we report that FoxA transcription factor family members FoxA1 and FoxA2 fuel cellular growth in breast cancer through the expression of a common target gene, namely the endothelial lipase (LIPG)
FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth.
Cell line
View SamplesHematopoietic Stem Cells (HSC) are originated during embryonic development from endothelial-like cells located in the ventral side of the dorsal aorta around day E10-12 of murine development. This region is called AGM for Aorta/Gonad/Mesonephros and refers to the tissues around the hemogenic aorta. Cells that emerge from the endothelium and show hematopoietic traits can be distinguished by the expression of the c-kit receptor and finally acquire the CD45 marker.
Hematopoietic stem cell development requires transient Wnt/β-catenin activity.
Specimen part
View SamplesContinuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced regulatory T cells. To decipher the molecular mechanisms governing this process, microarray data comparing highly (Ly-6C-) and lowly (Ly-6C+) Self-reactive naive CD4 T cells were obtained.
Calcium-mediated shaping of naive CD4 T-cell phenotype and function.
Specimen part
View SamplesSince bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions.
Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis.
Specimen part, Cell line
View SamplesTo find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sex, Specimen part
View SamplesThis study supports an active role for PLZF and RAR-PLZF in leukemogenesis, identifies upregulation of CRABPI as a novel mechanism contributing to retinoid resistance and reveals the ability of the reciprocal fusion gene products to mediate distinct
RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.
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View SamplesDe novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood fatality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models,we found that Asxl1 global loss or conditional deletion in osteoblasts and their progenitors in mice leads to significant bone loss and markedly decreased numbers of marrow mesenchymal stem/progenitor cells (MSPCs) compared with wild-type (WT) littermates. Asxl1-/- MSPCs displayed impaired self-renewal and skewed differentiation-away from osteoblasts and favoring adipocytes. RNA-seq analysis reveals the altered expression of genes involved in cell proliferation, skeletal development and morphogenesis. Furthermore, gene set enrichment analysis showed a decreased gene expression of stem cell self-renewal signature,suggesting the role of Asxl1 in regulating the stemness of MSPCs. Importantly, introducing Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1-/- MSPCs. Our study unveils a pivotal role of ASXL1 in maintenance of MSPC functions and skeletal development. Overall design: Examination of mRNA profiles in wild type and Asxl1-/- MSPCs by deep sequencing
Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell, Leading to Bohring-Opitz-like Syndrome in Mice.
Specimen part, Subject
View SamplesTransforming growth factor- (TGF-) is a key factor for the development of prostate cancer metastases in bone. In breast cancer and melanoma, studies have shown how TGF- regulates gene expression to allow cancer cells to adapt to the bone microenvironment.
The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone.
Specimen part, Cell line, Treatment
View SamplesCarcinoma development in colorectal cancer (CRC) is driven by genetic alterations in numerous signaling pathways. Alterations in the RAS-ERK1/2 pathway are associated with the shortest overall survival for patients after diagnosis of CRC metastatic disease, but how RAS-ERK signaling regulates CRC metastasis is still unknown.
ERK1/2 Signaling Induces Upregulation of ANGPT2 and CXCR4 to Mediate Liver Metastasis in Colon Cancer.
Cell line, Treatment
View SamplesGrb14 is an endogenous inhibitor of insulin signaling
Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance.
Specimen part, Treatment
View Samples