Abstract:
:Human colon carcinomas (CCs) represent a growing worldwide problem. One of the pathways that has been negatively implicated in the genesis of CCs is triggered by bone morphogenetic protein (BMP) ligands, which activate BMP receptors leading to the function of SMAD proteins in the nucleus. BMP signaling is altered in familial human polyposis, and mice with compromised BMP signaling in the intestine develop tumors. Here, we have re-evaluated the presence and roles of BMP signaling in advanced sporadic human CCs, using both primary tumors and established cell lines, and directly modulating BMP pathway activity in a cell-autonomous manner using constitutively active and dominant-negative BMP receptor Ib forms. We find evidence for active endogenous BMP signaling in all primary CC samples and for its role in promoting primary CC tumor growth and CC cell survival and proliferation in vivo in xenografts. In vitro, we also document autonomous and non-autonomous effects of enhanced BMP receptor activity on gap closure in culture, suggesting possible roles in invasion. Caution should thus be exerted in trying to augment or restore its activity for therapeutic purposes. In contrast, we raise the possibility that blockade of BMP signaling might have beneficial effects against at least a subset of advanced colon cancers.
journal_name
J Mol Cell Bioljournal_title
Journal of molecular cell biologyauthors
Lorente-Trigos A,Varnat F,Melotti A,Ruiz i Altaba Adoi
10.1093/jmcb/mjq035subject
Has Abstractpub_date
2010-12-01 00:00:00pages
318-32issue
6eissn
1674-2788issn
1759-4685pii
mjq035journal_volume
2pub_type
杂志文章abstract::Bacteria and archaea encode members of the large multiple antibiotic resistance regulator (MarR) family of transcriptional regulators. Generally, MarR homologs regulate activity of genes involved in antibiotic resistance, stress responses, virulence or catabolism of aromatic compounds. They constitute a diverse group ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq021
更新日期:2010-10-01 00:00:00
abstract::Scaffolding proteins play pivotal roles in the assembly of macromolecular machines such as the spliceosome. The adaptor protein CD2BP2, originally identified as a binding partner of the adhesion molecule CD2, is a pre-spliceosomal assembly factor that utilizes its glycine-tyrosine-phenylalanine (GYF) domain to co-loca...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv039
更新日期:2015-10-01 00:00:00
abstract::The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive si...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv052
更新日期:2015-10-01 00:00:00
abstract::Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated. We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis. In the curre...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjz056
更新日期:2019-09-19 00:00:00
abstract::Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery ba...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx017
更新日期:2017-08-01 00:00:00
abstract::Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targe...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy041
更新日期:2018-08-01 00:00:00
abstract::X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression. In female mammals, mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript (XIST) is essential for initiation of X chromosome inactivation upon differ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy074
更新日期:2019-09-19 00:00:00
abstract::The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we i...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw036
更新日期:2016-08-01 00:00:00
abstract::Histone deacetylase 1 (HDAC1) is an essential epigenetic regulator belonging to a highly conserved family of deacetylases. Increased HDAC1 activity and expression often correlates with neoplastic transformation. Here we show how specific modification of HDAC1 by SUMO1, but not by SUMO2, facilitates HDAC1 degradation. ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjt032
更新日期:2013-12-01 00:00:00
abstract::RAD9 regulates multiple cellular processes that influence genomic integrity, and for at least some of its functions the protein acts as part of a heterotrimeric complex bound to HUS1 and RAD1 proteins. RAD9 participates in DNA repair, including base excision repair, homologous recombination repair and mismatch repair,...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjq039
更新日期:2011-02-01 00:00:00
abstract::Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mju008
更新日期:2014-06-01 00:00:00
abstract::Embryonic stem cells (ESCs) exhibit unique chromatin features, including a permissive transcriptional program and an open, decondensed chromatin state. Induced pluripotent stem cells (iPSCs), which are very similar to ESCs, hold great promise for therapy and basic research. However, the mechanisms by which reprogrammi...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjr028
更新日期:2011-12-01 00:00:00
abstract::The ectoderm has the capability to generate epidermis and neuroectoderm and plays imperative roles during the early embryonic development. Our recent study uncovered a region with ectodermal progenitor potential in mouse embryo at embryonic day 7.0 and revealed that Nodal inhibition is essential for its formation. Her...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv030
更新日期:2015-10-01 00:00:00
abstract::Inactivation of the p53 gene is a key driver of tumorigenesis in various cancer cohorts and types. The quest for a successful p53-based therapy that holds the promise of treating more than half of the cancer population has culminated in extensive knowledge about the role and function of p53 and led to new proposed inn...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjz012
更新日期:2019-03-01 00:00:00
abstract::Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 g...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjt011
更新日期:2013-08-01 00:00:00
abstract::Type 2 immune response has been shown to facilitate cold-induced thermogenesis and browning of white fat. However, whether alternatively activated macrophages produce catecholamine and substantially promote adaptive thermogenesis in adipose tissue remains controversial. Here, we show that tyrosine hydroxylase (TyrH), ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx046
更新日期:2017-10-01 00:00:00
abstract::Motile cilia and flagella are microtubule-based organelles important for cell locomotion and extracellular liquid flow through beating. Although axonenal dyneins that drive ciliary beat have been extensively studied in unicellular Chlamydomonas, to what extent such knowledge can be applied to vertebrate is poorly know...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy043
更新日期:2019-05-01 00:00:00
abstract::Ever since gene targeting or specific modification of genome sequences in mice was achieved in the early 1980s, the reverse genetic approach of precise editing of any genomic locus has greatly accelerated biomedical research and biotechnology development. In particular, the recent development of the CRISPR/Cas9 system...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa060
更新日期:2020-10-30 00:00:00
abstract::HIV-Tat-interacting protein of 60 kDa (TIP60) is a lysine acetyltransferase and known to be downregulated in multiple cancers. Among various signalling pathways, TIP60 is implicated in regulating epithelial-mesenchymal transition (EMT). Here, we show that TIP60 expression abrogates cell migration and metastatic potent...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw038
更新日期:2016-10-01 00:00:00
abstract::E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lif...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv046
更新日期:2016-02-01 00:00:00
abstract::Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx059
更新日期:2017-12-01 00:00:00
abstract::The involvement of microRNAs (miRNAs) in the development of the neural crest (NC) cells and other neuronal differentiation is still poorly understood. Here, we investigated the global function of miRNAs in embryonic development by examining the Wnt1-cre-mediated Dicer knockout mice. Dicer ablation resulted in malforma...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq008
更新日期:2010-06-01 00:00:00
abstract::Deregulation of microRNAs (miRNAs) and c-Myc (Myc) contributes to hepatocellular carcinoma (HCC) progression, but how miRNAs and Myc regulate each other in hepatocarcinogenesis is still poorly understood. Using a functional screen, we identified miR-129-5p as a miRNA that inhibits HCC cell growth. miR-129-5p targets t...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw010
更新日期:2016-10-01 00:00:00
abstract::Mesoangioblasts (MABs) are vessel-associated stem cells that express pericyte marker genes and participate in skeletal muscle regeneration. Molecular circuits that regulate the myogenic commitment of MABs are still poorly characterized. The critical role of bone morphogenetic protein (BMP) signalling during proliferat...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv059
更新日期:2016-02-01 00:00:00
abstract::The MYC transcription factor plays a key role in cell growth control. Enhanced MYC protein stability has been found to promote tumorigenesis. Thus, understanding how MYC stability is controlled may have significant implications for revealing MYC-driven growth regulatory mechanisms in physiological and pathological pro...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjz098
更新日期:2020-07-03 00:00:00
abstract::Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa016
更新日期:2020-09-01 00:00:00
abstract::Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa058
更新日期:2020-10-26 00:00:00
abstract::We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immu...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjz104
更新日期:2020-05-18 00:00:00
abstract::Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs (lncRNAs). Emerging evidence indicates that lncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of lncRNAs is often associated with a variety of human diseases inclu...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mju013
更新日期:2014-06-01 00:00:00
abstract::Homoeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photoreceptors. The major fly rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how t...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw041
更新日期:2017-04-01 00:00:00