Abstract:
:Parathyroid hormone-related protein (PTHrP) is a critical regulator of bone resorption and augments osteolysis in skeletal malignancies. Here we report that the mature PTHrP1-36 hormone is processed by matrix metalloproteinases to yield a stable product, PTHrP1-17. PTHrP1-17 retains the ability to signal through PTH1R to induce calcium flux and ERK phosphorylation but not cyclic AMP production or CREB phosphorylation. Notably, PTHrP1-17 promotes osteoblast migration and mineralization in vitro, and systemic administration of PTHrP1-17 augments ectopic bone formation in vivo. Further, in contrast to PTHrP1-36, PTHrP1-17 does not affect osteoclast formation/function in vitro or in vivo. Finally, immunoprecipitation-mass spectrometry analyses using PTHrP1-17-specific antibodies establish that PTHrP1-17 is indeed generated by cancer cells. Thus, matrix metalloproteinase-directed processing of PTHrP disables the osteolytic functions of the mature hormone to promote osteogenesis, indicating important roles for this circuit in bone remodelling in normal and disease contexts.
journal_name
Oncogenejournal_title
Oncogeneauthors
Frieling JS,Shay G,Izumi V,Aherne ST,Saul RG,Budzevich M,Koomen J,Lynch CCdoi
10.1038/onc.2017.70subject
Has Abstractpub_date
2017-08-01 00:00:00pages
4498-4507issue
31eissn
0950-9232issn
1476-5594pii
onc201770journal_volume
36pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Mdm2, a regulator of the p53 tumor suppressor, is frequently overexpressed in lymphomas, including lymphomas that have inactivated p53. However, the biological consequences of Mdm2 overexpression in lymphocytes are not fully resolved. Here, we report that increased expression of Mdm2 in B cells augmented proliferation...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210788
更新日期:2008-03-06 00:00:00
abstract::Polymerase chain reaction (PCR) analysis of microsatellite polymorphisms corresponding to four loci which map to chromosome 17p and 11 loci which map to chromosome 17q was performed to screen for loss of heterozygosity (LOH) in paired normal and tumor tissues from 27 cases of borderline epithelial ovarian tumors (BEOT...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-05-16 00:00:00
abstract::Trichostatin A (TSA), a histone deacetylase inhibitor, strongly increases acetylation of the N-terminal tails of histone H3. Many studies have correlated the function of TSA with the hyperacetylation of histone. Although histone H3 is known to be phosphorylated, the effect of acetylation on phosphorylation is not know...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206507
更新日期:2003-08-14 00:00:00
abstract::We have previously reported that platelet-derived growth factor (PDGF) induced tyrosine phosphorylation of GTPase-activating protein (GAP) in intact quiescent fibroblasts under conditions in which insulin and basic fibroblast growth factor (bFGF) were ineffective (Molloy et al., 1988). In the present study, we have pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Loss of heterozygosity on chromosome 10p was observed frequently in human prostate cancers. Studies have demonstrated that the introduction of the short arm of human chromosome 10 into a human prostate cancer cell line, PPC-1, by microcell-mediated chromosome transfer (MMCT), suppressed the malignant phenotype, sugges...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204079
更新日期:2001-01-18 00:00:00
abstract::Somatic RET mutations have been identified in a variable proportion (about 30-70%) of sporadic Medullary Thyroid Carcinoma (MTC) cases. They are represented by the Met918Thr substitution (exon 16) typical of Multiple Endocrine Neoplasia type 2B (MEN2B) and, to a lesser extent, by nucleotide changes occurring at one of...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201079
更新日期:1997-05-29 00:00:00
abstract::Previous observations suggest expression of cyclooxygenase-2 to convey macrophage protection towards apoptotic cell death. We reasoned prostaglandin formation and in turn a cAMP increase as the underlying protective principle. Here we report that exposure of macrophages to lipopolysaccharide/interferon-gamma or lipoph...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201926
更新日期:1998-07-23 00:00:00
abstract::Sp1 is important for the transcription of many genes. Our previous studies have shown that Sp1 is degraded in normal cell, but it is preserved in cancer cells during mitosis and exists a priori in the daughter cells, ready to engage in gene transcription and thereby contributes to the proliferation and survival of can...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.649
更新日期:2012-11-22 00:00:00
abstract::The Kruppel-like transcription factor KLF6 is a novel tumor-suppressor gene mutated in a significant fraction of human prostate cancer. It is localized to human chromosome 10p14-15, a region that displays frequent loss of heterozygosity in glioblastoma multiforme (GBM). Indeed, mutations of the KLF6 gene have recently...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207662
更新日期:2004-06-24 00:00:00
abstract::The antifolates were the first class of antimetabolites to enter the clinics more than 50 years ago. Over the following decades, a full understanding of their mechanisms of action and chemotherapeutic potential evolved along with the mechanisms by which cells develop resistance to these drugs. These principals served ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1206946
更新日期:2003-10-20 00:00:00
abstract::E2F transcription factors are important regulators of the cell cycle, and unrestrained activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. Although highly expressed in normal skin and skin cancer, the role of the atypical E2Fs, E2F7 and E2F8, in keratin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.251
更新日期:2017-02-09 00:00:00
abstract::Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human m...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/s41388-019-1124-8
更新日期:2020-03-01 00:00:00
abstract::The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1279-3
更新日期:2020-05-01 00:00:00
abstract::The post-translational modifications ubiquitination and sumoylation have been implicated in regulating many critical cellular pathways. Like ubiquitination, sumoylation is a multistep process involving maturation, activation, conjugation and deconjugation. Ubc9 is a sole E2-conjugating enzyme essential for sumoylation...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208210
更新日期:2005-04-14 00:00:00
abstract::Clinical and experimental evidence is consistent with a key role for transforming human papilloma viruses (HPVs) in the aetiology of anogenital carcinoma. Cervical carcinoma does, however, occasionally occur in the absence of HPV sequences (Riou et al., 1990). We have used a direct cDNA/PCR sequencing protocol to anal...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::MyD88 was first characterized as a myeloid differentiation primary response gene in mice, activated in M1 myeloleukemic cells following interleukin-6 (IL-6) induced growth arrest and terminal differentiation. Analysis of expressed sequence tags (ESTs) from activated dendritic cell libraries led to the indentification ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-12-05 00:00:00
abstract::Mutations of the retinoblastoma tumor-suppressor gene (RB1) or components regulating the CDK-RB-E2F pathway have been identified in nearly every human malignancy. Re-establishing cell cycle control through cyclin-dependent kinase (CDK) inhibition has therefore emerged as an attractive option in the development of targ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2016.32
更新日期:2016-09-15 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and an aberrant microbiota of the lung. Microbial colonization contributes to chronic neutrophilic inflammation in COPD. Nontypeable Haemophilus influenzae (NTHi) is frequently found in lungs of stable COPD patients and i...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.28
更新日期:2017-07-20 00:00:00
abstract::During the evolution into castration or therapy resistance, prostate cancer cells reprogram the androgen responses to cope with the diminishing level of androgens, and undergo metabolic adaption to the nutritionally deprived and hypoxia conditions. AR (androgen receptor) and PKM2 (pyruvate kinase M2) have key roles in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0414-x
更新日期:2019-01-01 00:00:00
abstract::Glioblastoma is the most common and lethal primary malignant brain tumor in adults. The tumor suppressor gene PTEN is deleted, mutated or hypermethylated in more than 60% of glioblastoma cases resulting in hyperactivation of the phosphoinositide 3-kinase pathway, which leads to sustained PI(3,4,5)P3 signaling, and the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.303
更新日期:2015-07-01 00:00:00
abstract::Ewing sarcoma (ES) is an aggressive bone and soft tissue tumor of children and young adults in which finding effective new targeted therapies is imperative. Here, we report an in-depth preclinical study of the investigational cullin-RING ubiquitin ligase (CRL) inhibitor MLN4924 in ES, as we have recently demonstrated ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.153
更新日期:2013-03-14 00:00:00
abstract::Much evidence has been gathered in support of a critical role for p53 in the cellular response to DNA damage. p53 dysfunction is associated with progression and poor prognosis of many human cancers and with a high incidence of tumours in p53 knockout mice. The absence of a p53-dependent G1 arrest that facilitates DNA ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200871
更新日期:1997-02-06 00:00:00
abstract::The exact functions of BRCA1 have not been fully described but it now seems apparent that it has roles in DNA damage repair, transcriptional regulation, cell cycle control and most recently in ubiquitylation. These functions of BRCA1 are most likely interdependent but this review will focus on the role of BRCA1 in rel...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209872
更新日期:2006-09-25 00:00:00
abstract::Previous work by others has revealed homology between the rel oncogene and the transcription factor NF-kappa B. Further, in vitro-translated v-rel protein and c-rel protein are able to bind to an oligonucleotide containing the kappa B binding site. Unlike the in vitro-translated product, cellular Rel protein exists in...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that medi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.294
更新日期:2016-05-05 00:00:00
abstract::Ubiquitin-conjugation targets numerous cellular regulators for proteasome-mediated degradation. Thus, the identification of ubiquitin ligases and their physiological substrates is crucially important, especially for those cases in which aberrant levels of regulatory proteins (e.g., beta-catenin, p27) result from a der...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202653
更新日期:1999-01-28 00:00:00
abstract::Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC forma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.73
更新日期:2017-08-01 00:00:00
abstract::Interleukin-8 (IL-8), a chemokine implicated in the metastasis and angiogenesis of a variety of cancers, has been reported to be overexpressed in prostate cancer. In this study, we ascribe a new role for IL-8 in prostate cancer progression using LNCaP cells. We demonstrate that IL-8 activates the androgen receptor and...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207344
更新日期:2004-03-18 00:00:00
abstract::In an effort to understand the mechanisms governing the regulation of the mouse Ron receptor gene, a mouse genomic library was screened and overlapping clones coding for the Ron gene and flanking DNA were identified. Continuous DNA sequence was obtained for approximately 16.4 kilobases. The gene, from the initiator me...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201508
更新日期:1998-01-08 00:00:00
abstract::The IGF2 gene, which encodes a growth factor, is subject to genomic imprinting. The frequently observed loss of IGF2 imprinting in a variety of tumors has been suggested to contribute to neoplasia. Since these reports have not documented the imprinting status of IGF2 at the cellular level, it cannot be excluded that t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201501
更新日期:1998-01-08 00:00:00