EGAGenomicsIllumina HiSeq 2000;ILLUMINAhttps://ega-archive.org/datasets/EGAD0000100315414EGA dataset EGAD00001003154EGAMutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS.Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance.Walia Mannu K MK, Ho Patricia Mw PM, Taylor Scott S, Ng Alvin Jm AJ, Gupte Ankita A, Chalk Alistair M AM, Zannettino Andrew Cw AC, Martin T John TJ, Walkley Carl R CRTotal RNA Sequencing, WHOLE TRANSCRIPTOME SEQUENCING, Whole Transcriptome Shotgun Sequencing, RNA Sequencing, Transcriptome Sequencing, WTSS, RNA-Seq, Total RNA-Seq, RNA-seq (transcriptome sequencing), RNAseq, Whole-Transcriptome Sequencing, Whole Transcriptome Sequencing.Whole Transcriptome Shotgun Sequencing, study., RNA-seqbeta[[3]]-Tub, Osteosarcoma of bone (disorder), Osteochondrosarcoma, CRAMP, DmelCG17117, dp53, Osteogenic Sarcomas, p50, FALL39, 5'-cyclic monophosphate, p53, 143391_i_at, beta3 TU, Tumor, LFS1, betaTub3, PTH-Related Peptide, Tp53, l(3)05745, 5'-Cyclic AMP, AV083133, Osteogenic Sarcoma, PTHrP[38-94], DMP53, Cyclic adenylic acid, PTHR, bbl, CAP-18, Dmp53, anon-EST:Liang-2.13, Osteoblastic osteosarcoma, C13orf8, Parathyroid Hormone Related Peptide, Sarcomas, 1323/07, PTHrP[107-139], clone 2.13, BCC7, HHM, cAMP, Creb, D.m.BETA-60D, Sarcoma of Bone, PTH-Like Protein, BDE2, beta-Tub6D, dmp53, PTH Like Protein, ZNF828, CREB, 3', T, DmP53, 1422/04, Hypercalcemic Factor, Osteoblastic sarcoma, Osseous Sarcoma, Parathyroid Hormone Like Tumor Factor, B3t, DmelCG3401, Sarcoma, Trp53, Parathyroid Hormone-Like Protein, PTH Related Peptide, Dp53, no ICD-O subtype (morphologic abnormality), PTHrP, betaTub60C, Parathyroid hormone-like protein, PTH-like, beta3-tubulin, Parathyroid Hormone-Related Peptide, beta[[3]]-tubulin, TRP53, CG17117, p50/tubulin, single organism signaling, Tumors, HSD26, beta-Tub60D, PTH-rP, CG10873, Osteosarcoma of bone, Dmbeta3, Dm-HTH, 3526402H21Rik, Osteogenic sarcoma, Osteosarcoma - disorder, PTHRP, 2310001E10Rik, BETA 60D, prac, beta3t, beta3-Tub, CAP18, Osteostatin, Osteogenic, 5'-phosphate, CAMP, Pthrp, Xp53, 3t, Tumor Hypercalcemic Factor, Cyclic AMP, 5'-cyclic phosphate, [M]Osteosarcoma NOS, p53/tubulin, NOS, bfy, beta[[3]] tubulin, activation, PTHrP[1-36], Tub60D, HTH, Hth, Osteosarcomas, Parathyroid Hormone Like Protein, CG33336, Skeletal sarcoma, Bone Sarcoma, beta-tub, Sarcoma of the Bone, LL37, FALL-39, CHAMP, Hormone-Related Protein, DmelCG33336, D-p53, beta60C, osteoid sarcoma, CG3401, initiation, Maintenances., beta3Tub, beta3TUB, PLP, 5'-(hydrogen phosphate), Dm-P53, l(3)86Ca, Osteosarcoma, beta3, Creb-1, 5'-CYCLIC-MONOPHOSPHATE, Parathyroid, dtl, bone tissue neoplasm, Tub, DTB3, PTH Like Tumor Factor, Meis1, hth1, hth2, no ICD-O subtype, signalling process, betatub60D, Hypercalcemic Hormone of Malignancy, Adenosine 3', ADENOSINE-3', P53, p44, Parathyroid Hormone Related Protein, bhy, Osteosarcoma Tumors, Osteosarcoma Tumor, adenosine 3', CG31325, betaTub, osteosarcomaOsteochondrosarcoma, dp53, bone tumor, Osteogenic Sarcomas, single-organism developmental process, FALL39, 5'-cyclic monophosphate, postnatal development, growth and development, osseous tumour, Tumor, betaTub3, Tp53, Mutations, Osteogenic Sarcoma, DMP53, Extrinsic Pathway Apoptoses, PTHR, bbl, CAP-18, Dmp53, C13orf8, average, 1323/07, PTHrP[107-139], Man (Taxonomy), BCC7, cAMP, PTH-Like Protein, beta-Tub6D, BDE2, dmp53, PTH Like Protein, ZNF828, T, 3', DmP53, 1422/04, elevated, Hypercalcemic Factor, Osseous Sarcoma, B3t, DmelCG3401, Sarcoma, Intrinsic Pathway Apoptosis, high frequency, Parathyroid Hormone-Like Protein, Dp53, malignant neoplasm, no ICD-O subtype (morphologic abnormality), Classic, signaling process, Classical Apoptosis, osseous tumor, PTH-like, Malignancies, CG17117, p50/tubulin, single organism signaling, Tumors, HSD26, CG10873, PTH-rP, 3526402H21Rik, Caspase-Dependent Apoptosis, Osteosarcoma - disorder, PTHRP, Modern, Bone Neoplasm, CAP18, Osteogenic, bone tumour, 5'-phosphate, results, CAMP, Pthrp, 3t, Benign, signaling (initiator) caspase activity, Tumor Hypercalcemic Factor, Cyclic AMP, induction of apoptosis, Intrinsic Pathway, Extrinsic Pathway Apoptosis, NOS, bfy, Caspase-Dependent, Tub60D, PTHrP[1-36], activation, HTH, Hth, Osteosarcomas, beta-tub, Sarcoma of the Bone, absence, CHAMP, DmelCG33336, osteoid sarcoma, CG3401, beta3Tub, beta3TUB, Benign Neoplasms, common, Osteosarcoma, Cancer of Bone, Creb-1, human, bone tissue neoplasm, Parathyroid, Malignant Neoplasms, loss of, Intrinsic Pathway Apoptoses, DTB3, PTH Like Tumor Factor, hth1, hth2, induction of apoptosis by p53, Proliferation, Adenosine 3', P53, p44, Extrinsic Pathway, bhy, Osteosarcoma Tumors, Classical, CG31325, Bone, adenosine 3', Apoptoses, betaTub, osteosarcoma, beta[[3]]-Tub, Osteosarcoma of bone (disorder), Proliferating, CRAMP, DmelCG17117, biological signaling, human being, p50, Neoplasms, p53, caspase-dependent programmed cell death, Benign Neoplasm, Caspase Dependent Apoptosis, stalk, 143391_i_at, beta3 TU, LFS1, Malignant, bone neoplasm, PTH-Related Peptide, l(3)05745, Human, 5'-Cyclic AMP, AV083133, PTHrP[38-94], Homo sapiens, Cyclic adenylic acid, anon-EST:Liang-2.13, Osteoblastic osteosarcoma, Type I, Man, Cancer of the Bone, Parathyroid Hormone Related Peptide, Sarcomas, clone 2.13, Malignancy, HHM, Creb, D.m.BETA-60D, Sarcoma of Bone, proliferating, absent from organism, CREB, apoptosis activator activity, Osteoblastic sarcoma, culm, Neoplasias, Parathyroid Hormone Like Tumor Factor, Trp53, PTH Related Peptide, PTHrP, Classic Apoptosis, betaTub60C, Parathyroid hormone-like protein, beta3-tubulin, beta[[3]]-tubulin, Parathyroid Hormone-Related Peptide, TRP53, high elevation, Cancer, Apoptosis, beta-Tub60D, Osteosarcoma of bone, Dmbeta3, Dm-HTH, Malignant Neoplasm, Osteogenic sarcoma, 2310001E10Rik, axis, BETA 60D, prac, beta3t, beta3-Tub, Point Mutations, Osteostatin, Cell, Xp53, development, MT, 5'-cyclic phosphate, [M]Osteosarcoma NOS, p53/tubulin, Programmed Cell Death, Neoplasm, beta[[3]] tubulin, Mutation, C2., Parathyroid Hormone Like Protein, CG33336, Skeletal sarcoma, Bone Sarcoma, primary cancer, LL37, frequent, FALL-39, apoptosis, D-p53, postnatal growth, Hormone-Related Protein, beta60C, Dm-P53, l(3)86Ca, PLP, 5'-(hydrogen phosphate), beta3, Cancers, Osteoblast, malignant tumor, 5'-CYCLIC-MONOPHOSPHATE, dtl, signalling, Tub, Classic Apoptoses, Meis1, no ICD-O subtype, signalling process, betatub60D, Point, Isolation of Nuclei TAgged in specific Cell Types, Modern Man, Hypercalcemic Hormone of Malignancy, Bone Cancer, ADENOSINE-3', commitment to apoptosis, Osteosarcoma Tumor, Parathyroid Hormone Related Protein, growth, NeoplasiafalsePCGP OS RNASEQ - samplesRNA-Seq files for SJOS study2017-07-26 15:39:27EGAD00001003154960627070462EGAC00001000044EGAS00001000263