Abstract:
:The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K components represents one of the main goals to produce therapeutic agents. Here, we evaluated the efficacy of a phosphopeptide 1257 (P-1257) that targeting p85 strongly inhibits PI3K activity. We tested the effects of P-1257 administration in vitro and in vivo using BC cells expressing different levels of ErbB-2 and resistant or responsive to Trastuzumab. We demonstrated that inhibition of p85 activity by P-1257 induces cell death and sensitizes JIMT-1 and KPL-4 ErbB-2-overexpressing BC cells to Trastuzumab treatment. It is noteworthy that P-1257 delivery in vivo by electroporation or liposomes significantly inhibits the proliferation of tumor cells engrafted at subcutaneous and visceral sites. Overall, our data indicate that the p85 subunit is a valid target for therapeutic approaches and suggest that the structure of the peptide used in our study could be utilized for the development of novel drugs to apply in combination with therapies that fail to cure BCs with high PI3K activity.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Folgiero V,Di Carlo SE,Bon G,Spugnini EP,Di Benedetto A,Germoni S,Pia Gentileschi M,Accardo A,Milella M,Morelli G,Bossi G,Mottolese M,Falcioni Rdoi
10.1038/cddis.2012.179subject
Has Abstractpub_date
2012-12-06 00:00:00pages
e440issn
2041-4889pii
cddis2012179journal_volume
3pub_type
杂志文章abstract::Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1459-7
更新日期:2019-03-04 00:00:00
abstract::Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.41
更新日期:2011-05-19 00:00:00
abstract::The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. We elucidated this interesting question in pancreatic ductal adenocarcinoma, which...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.157
更新日期:2016-06-02 00:00:00
abstract::Cardiac glycosides (CGs), prescribed to treat cardiovascular alterations, display potent anti-cancer activities. Despite their well-established target, the sodium/potassium (Na(+)/K(+))-ATPase, downstream mechanisms remain poorly elucidated. UNBS1450 is a hemi-synthetic cardenolide derived from 2″-oxovorusharin extrac...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.134
更新日期:2015-06-11 00:00:00
abstract::MicroRNAs (miRNAs) are important class of functional regulators involved in human cancers development, including colorectal cancer (CRC). Exploring aberrantly expressed miRNAs may provide us with new insights into the initiation and development of CRC by functioning as oncogenes or tumor suppressors. The aim of our st...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1188-3
更新日期:2019-02-12 00:00:00
abstract::Senescence is an antiproliferative mechanism that can suppress tumor development and can be induced by oncogenes such as genes of the Ras family. Although studies have implicated bioactive sphingolipids (SL) in senescence, the specific mechanisms remain unclear. Here, using MCF10A mammary epithelial cells, we demonstr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03281-4
更新日期:2021-01-04 00:00:00
abstract::The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1354-2
更新日期:2019-02-12 00:00:00
abstract::Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays important roles in cell maintenance, expansion and differentiation. Removal of genes essential for autophagy from embryonic neural stem and precursor cells reduces the survival and inhibits neuronal differentiation of adult-generated neu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.406
更新日期:2016-03-03 00:00:00
abstract::Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mas...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1100-1
更新日期:2018-10-10 00:00:00
abstract::Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we rep...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2195-8
更新日期:2019-12-20 00:00:00
abstract::Back pain is a leading cause of global disability and is strongly associated with intervertebral disc (IVD) degeneration (IDD). Hallmarks of IDD include progressive cell loss and matrix degradation. The Akt signaling pathway regulates cellularity and matrix production in IVDs and its inactivation is known to contribut...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1985-3
更新日期:2019-10-03 00:00:00
abstract::Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substituti...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1333-7
更新日期:2019-02-11 00:00:00
abstract::We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and dist...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.262
更新日期:2015-10-15 00:00:00
abstract::The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03235-w
更新日期:2020-12-11 00:00:00
abstract::Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4(+) T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.327
更新日期:2013-09-05 00:00:00
abstract::Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor micr...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2509-x
更新日期:2020-05-04 00:00:00
abstract::Cervical cancer is the most common gynecological malignancy in the world; however, the survival rates of advanced-stage and recurrent cervical cancer patients remain poor. The multifaced protein insulin-like growth factor 2 receptor (IGF2R) has various ligands, represented as IGF-2 and mannose-6-phosphate (M6P)-tagged...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2117-9
更新日期:2019-11-20 00:00:00
abstract::Synovial sarcoma is a highly aggressive but rare form of soft tissue malignancy that primarily affects the extremities of the arms or legs, for which current chemotherapeutic agents have not been proven to be very effective. The cyclin-dependent kinase 4/6-retinoblastoma protein (CDK4/6-Rb) pathway of cell cycle contr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0474-4
更新日期:2018-05-01 00:00:00
abstract::Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2017.440
更新日期:2017-09-07 00:00:00
abstract::Protein-coding genes account for only ~2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs). A growing volume of literature has proposed that lncRNAs are important factors in cancer. Colon cancer-associated transcript-1 (CCAT1), an lncRNA, which ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.541
更新日期:2015-01-08 00:00:00
abstract::The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.574
更新日期:2015-01-22 00:00:00
abstract::It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.122
更新日期:2014-04-10 00:00:00
abstract::Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly incre...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.372
更新日期:2016-11-17 00:00:00
abstract::Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastogr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.554
更新日期:2017-10-26 00:00:00
abstract::Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been e...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2135-7
更新日期:2019-11-26 00:00:00
abstract::Bone metastasis is a severe complication of advanced breast cancer, resulting in osteolysis and increased mortality in patients. Raddeanin A (RA), isolated from traditional Chinese herbs, is an oleanane-type triterpenoid saponin with anticancer potential. In this study, we investigated the effects of RA in breast canc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0417-0
更新日期:2018-03-07 00:00:00
abstract::Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-se...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.38
更新日期:2015-02-26 00:00:00
abstract::G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflam...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0267-9
更新日期:2018-02-14 00:00:00
abstract::Dia1, which belongs to the diaphanous-related formin family, influences a variety of cellular processes through straight actin elongation activity. Recently, novel DIA1 mutants such as p.R1213X (p.R1204X) and p.A265S, have been reported to cause an autosomal dominant sensorineural hearing loss (DFNA1). Additionally, a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02743-z
更新日期:2020-07-16 00:00:00
abstract::Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.228
更新日期:2014-05-29 00:00:00