Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast.

Abstract:

:Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are controlled by the prolyl-isomerase Pin1. Mechanistically, following interaction with Pin1, Notch1 and Notch4, key regulators of cell fate, escape from proteasomal degradation by their major ubiquitin-ligase Fbxw7α. Functionally, we show that Fbxw7α acts as an essential negative regulator of breast CSCs' expansion by restraining Notch activity, but the establishment of a Notch/Pin1 active circuitry opposes this effect, thus promoting breast CSCs self-renewal, tumor growth and metastasis in vivo. In human breast cancers, despite Fbxw7α expression, high levels of Pin1 sustain Notch signaling, which correlates with poor prognosis. Suppression of Pin1 holds promise in reverting aggressive phenotypes, through CSC exhaustion as well as recovered drug sensitivity carrying relevant implications for therapy of breast cancers.

journal_name

EMBO Mol Med

journal_title

EMBO molecular medicine

authors

Rustighi A,Zannini A,Tiberi L,Sommaggio R,Piazza S,Sorrentino G,Nuzzo S,Tuscano A,Eterno V,Benvenuti F,Santarpia L,Aifantis I,Rosato A,Bicciato S,Zambelli A,Del Sal G

doi

10.1002/emmm.201302909

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

99-119

issue

1

eissn

1757-4676

issn

1757-4684

pii

emmm.201302909

journal_volume

6

pub_type

杂志文章
  • Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers.

    abstract::Mitochondrial disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We in...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201809091

    authors: Buzkova J,Nikkanen J,Ahola S,Hakonen AH,Sevastianova K,Hovinen T,Yki-Järvinen H,Pietiläinen KH,Lönnqvist T,Velagapudi V,Carroll CJ,Suomalainen A

    更新日期:2018-12-01 00:00:00

  • Vaccines for the 21st century.

    abstract::In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2-3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1002/emmm.201403876

    authors: Delany I,Rappuoli R,De Gregorio E

    更新日期:2014-06-01 00:00:00

  • Pathological impact of SMN2 mis-splicing in adult SMA mice.

    abstract::Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201302567

    authors: Sahashi K,Ling KK,Hua Y,Wilkinson JE,Nomakuchi T,Rigo F,Hung G,Xu D,Jiang YP,Lin RZ,Ko CP,Bennett CF,Krainer AR

    更新日期:2013-10-01 00:00:00

  • A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia.

    abstract::RAD51 recombinase activity plays a critical role for cancer cell proliferation and survival, and often contributes to drug-resistance. Abnormally elevated RAD51 function and hyperactive homologous recombination (HR) rates have been found in a panel of cancers, including breast cancer and chronic myeloid leukaemia (CML...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201201760

    authors: Zhu J,Zhou L,Wu G,Konig H,Lin X,Li G,Qiu XL,Chen CF,Hu CM,Goldblatt E,Bhatia R,Chamberlin AR,Chen PL,Lee WH

    更新日期:2013-03-01 00:00:00

  • Metronomic chemotherapy offsets HIFα induction upon maximum-tolerated dose in metastatic cancers.

    abstract::Conventional maximum-tolerated dose (MTD) chemotherapy relies on periodic, massive cancer cell ablation events followed by treatment-free intermissions, stereotypically resulting in resistance, relapse, and mortality. Furthermore, MTD chemotherapy can promote metastatic dissemination via activation of a transcriptiona...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911416

    authors: Schito L,Rey S,Xu P,Man S,Cruz-Muñoz W,Kerbel RS

    更新日期:2020-09-07 00:00:00

  • Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody.

    abstract::The angiopoietin (Ang)-Tie pathway has been intensely pursued as candidate second-generation anti-angiogenic target. While much of the translational work has focused on the ligand Ang2, the clinical efficacy of Ang2-targeting drugs is limited and failed to improve patient survival. In turn, the orphan receptor Tie1 re...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911164

    authors: Singhal M,Gengenbacher N,La Porta S,Gehrs S,Shi J,Kamiyama M,Bodenmiller DM,Fischl A,Schieb B,Besemfelder E,Chintharlapalli S,Augustin HG

    更新日期:2020-06-08 00:00:00

  • Dietary magnesium supplementation improves lifespan in a mouse model of progeria.

    abstract::Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+ ) showed an increased level of mitochondrial reactive oxygen species (ROS) and a reduced basal antioxidant capacity, including loss of the NADPH-coupled glutathione redox system....

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.202012423

    authors: Villa-Bellosta R

    更新日期:2020-10-07 00:00:00

  • A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases.

    abstract::Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201506078

    authors: Körbelin J,Dogbevia G,Michelfelder S,Ridder DA,Hunger A,Wenzel J,Seismann H,Lampe M,Bannach J,Pasparakis M,Kleinschmidt JA,Schwaninger M,Trepel M

    更新日期:2016-06-01 00:00:00

  • Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease.

    abstract::Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests tha...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.15252/emmm.201607260

    authors: Holmberg FE,Seidelin JB,Yin X,Mead BE,Tong Z,Li Y,Karp JM,Nielsen OH

    更新日期:2017-05-01 00:00:00

  • iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.

    abstract::Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogene...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708191

    authors: Hollingsworth EW,Vaughn JE,Orack JC,Skinner C,Khouri J,Lizarraga SB,Hester ME,Watanabe F,Kosik KS,Imitola J

    更新日期:2017-12-01 00:00:00

  • Adeno-associated virus-vectored influenza vaccine elicits neutralizing and Fcγ receptor-activating antibodies.

    abstract::The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has pro...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910938

    authors: Demminger DE,Walz L,Dietert K,Hoffmann H,Planz O,Gruber AD,von Messling V,Wolff T

    更新日期:2020-05-08 00:00:00

  • Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing.

    abstract::In the normal quiescent vasculature, only 0.01% of endothelial cells (ECs) are proliferating. However, this proportion increases dramatically following the angiogenic switch during tumor growth or wound healing. Recent evidence suggests that this angiogenic switch is accompanied by a metabolic switch. Here, we show th...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201303016

    authors: Coutelle O,Hornig-Do HT,Witt A,Andree M,Schiffmann LM,Piekarek M,Brinkmann K,Seeger JM,Liwschitz M,Miwa S,Hallek M,Krönke M,Trifunovic A,Eming SA,Wiesner RJ,Hacker UT,Kashkar H

    更新日期:2014-05-01 00:00:00

  • Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF.

    abstract::Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and prom...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201101107

    authors: Lee SW,Jeong HK,Lee JY,Yang J,Lee EJ,Kim SY,Youn SW,Lee J,Kim WJ,Kim KW,Lim JM,Park JW,Park YB,Kim HS

    更新日期:2012-09-01 00:00:00

  • Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function.

    abstract::Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced kinase1 (PINK1) are important causes of recessive Parkinson disease (PD). Studies on loss of function and overexpression implicate PINK1 in apoptosis, abnormal mitochondrial morphology, impaired dopamine release and motor deficits. However,...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.200900006

    authors: Morais VA,Verstreken P,Roethig A,Smet J,Snellinx A,Vanbrabant M,Haddad D,Frezza C,Mandemakers W,Vogt-Weisenhorn D,Van Coster R,Wurst W,Scorrano L,De Strooper B

    更新日期:2009-05-01 00:00:00

  • Targeting cardiac hypertrophy through a nuclear co-repressor.

    abstract::Heart failure entails the inability of the heart to pump blood to vital organs. One of the main risk factors for heart failure is the development of pathological hypertrophy. In this issue of EMBO Molecular Medicine, Li and coworkers show that NCoR1, a co-repressor of transcription factors, inhibits the transcriptiona...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.15252/emmm.201911297

    authors: Grund A,Heineke J

    更新日期:2019-11-07 00:00:00

  • Tumour growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin 3E isoform.

    abstract::Secreted Semaphorin 3E (Sema3E) promotes cancer cell invasiveness and metastatic spreading. The pro-metastatic activity of Sema3E is due to its proteolytic fragment p61, capable of transactivating the oncogenic tyrosine kinase ErbB2 that associates with the Sema3E receptor PlexinD1 in cancer cells. Here, we show that ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201100205

    authors: Casazza A,Kigel B,Maione F,Capparuccia L,Kessler O,Giraudo E,Mazzone M,Neufeld G,Tamagnone L

    更新日期:2012-03-01 00:00:00

  • Dissecting human antibody responses: useful, basic and surprising findings.

    abstract::Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target-agnostic approach based...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201808879

    authors: Lanzavecchia A

    更新日期:2018-03-01 00:00:00

  • A versatile drug delivery system targeting senescent cells.

    abstract::Senescent cells accumulate in multiple aging-associated diseases, and eliminating these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high lysosomal β-galactosidase activity of senescent cells to design a drug delivery system based on the encapsulation of drugs with gal...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201809355

    authors: Muñoz-Espín D,Rovira M,Galiana I,Giménez C,Lozano-Torres B,Paez-Ribes M,Llanos S,Chaib S,Muñoz-Martín M,Ucero AC,Garaulet G,Mulero F,Dann SG,VanArsdale T,Shields DJ,Bernardos A,Murguía JR,Martínez-Máñez R,Serrano M

    更新日期:2018-09-01 00:00:00

  • Genomic data sharing in Europe is stumbling-Could a code of conduct prevent its fall?

    abstract::Genomic data sharing is becoming more important as scientists join forces across borders in biomedical research for the benefit of patients and society. The EU's General Data Protection Regulation (GDPR) helps simplify sharing of such data at the European and international level. However, initial optimism has dried up...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911421

    authors: Molnár-Gábor F,Korbel JO

    更新日期:2020-03-06 00:00:00

  • A single epidermal stem cell strategy for safe ex vivo gene therapy.

    abstract::There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells be...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201404353

    authors: Droz-Georget Lathion S,Rochat A,Knott G,Recchia A,Martinet D,Benmohammed S,Grasset N,Zaffalon A,Besuchet Schmutz N,Savioz-Dayer E,Beckmann JS,Rougemont J,Mavilio F,Barrandon Y

    更新日期:2015-04-01 00:00:00

  • An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer.

    abstract::The prostate-specific membrane antigen (PSMA) has been demonstrated in numerous studies to be expressed specifically on prostate carcinoma cells and on the neovasculature of several other cancer entities. However, the simultaneous expression of PSMA on both, tumor cells as well as tumor vessels remains unclear, even i...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911902

    authors: Zekri L,Vogt F,Osburg L,Müller S,Kauer J,Manz T,Pflügler M,Maurer A,Heitmann JS,Hagelstein I,Märklin M,Hörner S,Todenhöfer T,Calaminus C,Stenzl A,Pichler B,la Fougère C,Schneider MA,Rammensee HG,Zender L,Sipos B,

    更新日期:2020-12-29 00:00:00

  • Increased VEGF-A promotes multiple distinct aging diseases of the eye through shared pathomechanisms.

    abstract::While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201505613

    authors: Marneros AG

    更新日期:2016-03-01 00:00:00

  • Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFβ.

    abstract::High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to ac...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910681

    authors: Germann M,Zangger N,Sauvain MO,Sempoux C,Bowler AD,Wirapati P,Kandalaft LE,Delorenzi M,Tejpar S,Coukos G,Radtke F

    更新日期:2020-01-09 00:00:00

  • Google's Project Nightingale highlights the necessity of data science ethics review.

    abstract::On November 14 last year, the British Guardian published an account from an anonymous whistleblower at Google, accusing the company of misconduct in regard to handling sensitive health data. The whistleblower works for Project Nightingale, an attempt by Google to get into the lucrative US healthcare market, by storing...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.202012053

    authors: Schneble CO,Elger BS,Shaw DM

    更新日期:2020-03-06 00:00:00

  • Transparency and accountability.

    abstract::EMBO Molecular Medicine is enriched by a number of innovative policies designed to enhance the editorial process: peer review process files, de-emphasis of confidential referee comments and cross-refereeing. ...

    journal_title:EMBO molecular medicine

    pub_type: 社论

    doi:10.1002/emmm.201000094

    authors: Pulverer B

    更新日期:2010-09-01 00:00:00

  • Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens.

    abstract::Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sust...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201000093

    authors: Smith KM,Datti A,Fujitani M,Grinshtein N,Zhang L,Morozova O,Blakely KM,Rotenberg SA,Hansford LM,Miller FD,Yeger H,Irwin MS,Moffat J,Marra MA,Baruchel S,Wrana JL,Kaplan DR

    更新日期:2010-09-01 00:00:00

  • TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance.

    abstract::Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid β-peptide (Aβ) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201606370

    authors: Xiang X,Werner G,Bohrmann B,Liesz A,Mazaheri F,Capell A,Feederle R,Knuesel I,Kleinberger G,Haass C

    更新日期:2016-09-01 00:00:00

  • Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1.

    abstract::Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-c...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708347

    authors: Patel R,Fleming J,Mui E,Loveridge C,Repiscak P,Blomme A,Harle V,Salji M,Ahmad I,Teo K,Hamdy FC,Hedley A,van den Broek N,Mackay G,Edwards J,Sansom OJ,Leung HY

    更新日期:2018-04-01 00:00:00

  • Heat shock factor 2 is a stress-responsive mediator of neuronal migration defects in models of fetal alcohol syndrome.

    abstract::Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal and Hsf2-deficient mice and cell systems to uncover a pivotal role for heat shock...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201303311

    authors: El Fatimy R,Miozzo F,Le Mouël A,Abane R,Schwendimann L,Sabéran-Djoneidi D,de Thonel A,Massaoudi I,Paslaru L,Hashimoto-Torii K,Christians E,Rakic P,Gressens P,Mezger V

    更新日期:2014-08-01 00:00:00

  • SIL1, a causative cochaperone gene of Marinesco-Söjgren syndrome, plays an essential role in establishing the architecture of the developing cerebral cortex.

    abstract::Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 muta...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201303069

    authors: Inaguma Y,Hamada N,Tabata H,Iwamoto I,Mizuno M,Nishimura YV,Ito H,Morishita R,Suzuki M,Ohno K,Kumagai T,Nagata K

    更新日期:2014-03-01 00:00:00