Abstract：
:The ERBB1/2/4 inhibitor neratinib causes plasma membrane-associated K-RAS to mislocalize into intracellular vesicles; this effect is enhanced by HDAC inhibitors and the combination of [neratinib + sodium valproate] is now a phase I trial (NCT03919292). The present studies were performed to understand resistance mechanisms that evolve following [neratinib + valproate] exposure. Exposure of pancreatic tumor cells to [neratinib + sodium valproate] initially reduced the expression and phosphorylation of ERBB family receptors, c-MET and c-KIT. Following a 24 h drug exposure and a further 24 h culture in drug free conditions, the effects on c-MET, c-KIT and most ERBB family receptors had returned to near baseline levels. However, the expression and phosphorylation of ERBB3 were increased which was associated with elevated AKT T308 phosphorylation. Knock down of ERBB3 significantly enhanced [neratinib + valproate] lethality, which was associated with greater inactivation of AKT, mTOR, p70 S6K and ERK1/2. The PI3Kα/δ inhibitor copanlisib also significantly enhanced killing after [neratinib + valproate] exposure. Copanlisib enhanced [neratinib + valproate] lethality via autophagosome formation and autophagic flux. Our data argue for further in vivo exploration as to whether copanlisib can be safely combined with [neratinib + valproate].
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Dent P,Booth L,Poklepovic A,Hoff DV,Hancock JFdoi
10.1016/j.cellsig.2020.109525subject
Has Abstractpub_date
2020-04-01 00:00:00pages
109525eissn
0898-6568issn
1873-3913pii
S0898-6568(20)30002-4journal_volume
68pub_type
杂志文章abstract：:Skeletal muscle is highly adapted to respond to oxidative imbalances, since it is continuously subjected to an increased production of reactive oxygen species (ROS) during exercise. Oxidative stress, however, has been associated with skeletal muscle atrophy and damage in many diseases. In this study, we examined wheth...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.05.004
更新日期：2006-12-01 00:00:00
abstract：:Perivascular adipocyte (PVAC) biofunctions were closely related to cardiovascular diseases; its specific biological mechanisms remained unclear. How to adjust PVAC functions of vascular cells is an important topic. The present study was designed to investigate whether FAK/Pyk2 and ERK1/2 MAPK signaling pathways partic...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.09.017
更新日期：2014-12-01 00:00:00
abstract：:Mechanical stretch is an initial factor for cardiac hypertrophy in response to haemodynamic overload (high blood pressure). Stretch of cardiomyocytes activates second messengers such as phosphatidylinositol, protein kinase C, Raf-1 kinase and extracellular signal-regulated protein kinases (ERKs), which are involved in...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(98)00036-9
更新日期：1998-11-01 00:00:00
abstract：:Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PC...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.06.002
更新日期：2016-09-01 00:00:00
abstract：:The transcription factor Egr-1 is encoded by an immediate early response gene and has been shown to be a key regulator in the induction of apoptosis, mitogenesis and differentiation. It is rapidly induced by different stimuli including the glycoprotein hormone erythropoietin. In this report, we analyse the role of dif...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.06.013
更新日期：2008-10-01 00:00:00
abstract：:Desensitization of the micro-opioid receptor (MOR) has been implicated as an important regulatory process in the development of tolerance to opiates. Monitoring the release of intracellular Ca(2+) ([Ca(2+)](i)), we reported that [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO)-induced receptor desensitization req...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.12.003
更新日期：2010-04-01 00:00:00
abstract：:The peroxisome proliferator-activated receptor (PPAR) family was discovered from an orphan nuclear receptor approach, and thereafter, three subtypes were identified, namely PPARalpha, PPARbeta or PPARgamma and PPARgamma. The two former seem to regulate lipid homeostasis, whereas the latter is involved, among others, i...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(01)00281-9
更新日期：2002-07-01 00:00:00
abstract：:Characterization of cardiac MYPT2 (an isoform of the smooth muscle phosphatase [MP] target subunit, MYPT1) is described. Several features of MYPT2 and MYPT1 were similar, including: a specific interaction with the catalytic subunit of type 1 phosphatase, delta isoform (PP1cdelta); interaction of MYPT2 with the small h...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.11.001
更新日期：2006-09-01 00:00:00
abstract：:Recent global incidences and mortality rates have placed colorectal cancer (CRC) at third and second positions, respectively, among both sexes of all ages. Resistance during chemotherapy is a big problem in the treatment and disease-free survival of CRC patients. Discovery of new anticancer drug(s) is a time taking pr...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109803
更新日期：2020-12-01 00:00:00
abstract：PURPOSE:Our study aimed to study the role of lncRNA TP73-AS1/miR-539/MMP-8 axis in modulating M2 macrophage polarization in hepatocellular carcinoma (HCC). METHODS:The gene expression levels of TP73-AS1, miR-539 and MMP-8 were modified by transfection with the overexpression or knockdown vectors. The patient survival ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109738
更新日期：2020-11-01 00:00:00
abstract：:Cardiac hypertrophy is accompanied by excessive collagen deposition in the heart. Despite painstaking research on this fatal disease, the precise role of molecular chaperones in myocardial fibrosis has not yet been elucidated. In this study, we have analyzed the mechanism by which Heat shock protein 90 (Hsp90)/Cell di...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.09.005
更新日期：2015-12-01 00:00:00
abstract：:The effects of ouabain and monensin upon basal and carbachol-stimulated inositol phospholipid breakdown in rat cerebral cortical miniprisms have been investigated. Basal inositol phospholipid breakdown was increased by both compounds at both 6 and 18 mM K+. Enhancement of the carbachol response at 6 mM, but not at 18 ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(91)90046-w
更新日期：1991-01-01 00:00:00
abstract：:Major diseases such as cardiovascular diseases, rheumatoid arthritis, diabetes, obesity and tumor growth are known to involve inflammation. Inflammatory molecules such as MCP-1, TNF-α, IL-1β and IL-8 are known to promote angiogenesis. MCP-induced protein (MCPIP), originally discovered as a novel zinc finger protein in...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.07.014
更新日期：2012-11-01 00:00:00
abstract：:Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca(2+) activated Cl(-) channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.09.001
更新日期：2014-12-01 00:00:00
abstract：:We assign a new function to a tumor suppressor NPRL2 that activates the mTOR complex 1 (mTORC1) activity. The positive regulation of mTORC1 activity by NPRL2 is mediated through NPRL2 interaction with Raptor. While NPRL2 interacts with Rag GTPases, RagD in particular, to interfere with mTORC1 activity in amino acid sc...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.11.008
更新日期：2016-02-01 00:00:00
abstract：:Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative multifactorial disease characterized, like other diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) or frontotemporal dementia (FTD), by the degeneration of specific neuronal cell populations. Motor neuron loss is distinctive of ALS. However, ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.05.016
更新日期：2010-10-01 00:00:00
abstract：:CK1δ and CK1ε are unique in the casein kinase 1 family and play critical roles in a number of physiological intracellular pathways. In particular, these kinases are involved in composing the mammalian circadian clock by phosphorylating core clock proteins. Considering that CK1δ/ε phosphorylate other key biological mol...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2016.12.010
更新日期：2017-02-01 00:00:00
abstract：:Antidepressants are commonly used in the treatment of anxiety and depression, medical conditions that affect approximately 17-20% of the population. The clinical effects of antidepressants take several weeks to manifest, suggesting that these drugs induce adaptive changes in brain structures affected by anxiety and de...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2004.12.007
更新日期：2005-05-01 00:00:00
abstract：:In this study we investigated the release of Ca2+ in brain microsomes after Ca2+ loading by the Ca(2+)-ATPase or by the Na+/Ca2+ exchanger. The results show that in microsomes loaded with Ca2+ by the Ca(2+)-ATPase, Ins(1,4,5)P3 (5 microM) released 21 +/- 2% of the total Ca2+ accumulated, and that in the microsomes loa...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(92)90049-e
更新日期：1992-11-01 00:00:00
abstract：:The BRCA1 gene codes for a protein involved in the DNA double strand break (DDSB) repair. Alongside the dominant full-length splicing form of BRCA1, numerous endogenously expressed alternative splicing variants of unknown significance have been described in various tissues. Some of them retain the original BRCA1 readi...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.12.023
更新日期：2012-05-01 00:00:00
abstract：:Protein kinase CK2 is a highly conserved, pleiotropic, protein serine/threonine kinase that is essential for life in eukaryotes. CK2 has been implicated in diverse cellular processes such as cell cycle regulation, circadian rhythms, apoptosis, transformation and tumorigenesis. In addition, there is increasing evidence...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2005.07.008
更新日期：2006-03-01 00:00:00
abstract：:Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.04.003
更新日期：2014-08-01 00:00:00
abstract：:Hydrogen peroxide (H(2)O(2)) mediates induction of cytotoxicity in various cell types. GSK-3beta has been found to participate in a number of signaling pathways, including cell proliferation and cell death. In the present study, we show that GSK-3beta is rapidly dephosphorylated and activated in response to H(2)O(2) t...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.06.001
更新日期：2006-05-01 00:00:00
abstract：:Chemotaxis plays an important role in metastasis of cancer cells. In the current study, we investigated the role of PTEN, a tumor suppressor, in chemotaxis of human breast cancer cells. Over-expression of PTEN inhibited EGF-induced chemotaxis, probably due to an overall reduction of PIP(3) levels. Disruption of PTEN b...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2007.06.007
更新日期：2007-11-01 00:00:00
abstract：:A critical aspect of understanding the regulation of signal transduction is not only to identify the protein-protein interactions that govern assembly of signaling pathways, but also to understand how those pathways are regulated in time and space. In this report, we have applied both gain-of-function and loss-of-func...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.06.006
更新日期：2018-10-01 00:00:00
abstract：:The transforming growth factor beta (TGFbeta) family of growth regulatory peptides plays an important role in the regulation of gastrointestinal epithelial cell homeostasis. Loss of growth inhibitory signalling by TGFbeta is common in the context of Ras-transformation and it has been hypothesized that loss of TGFbeta ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(03)00010-x
更新日期：2003-07-01 00:00:00
abstract：:G protein-coupled receptors (GPCRs) can engage multiple pathways to activate ERK1/2 via both G proteins and/or ßarrestin. Receptor recruitment of ßarrestin is also important for GPCR desensitization, internalization and resensitization. Modulation of the receptor/ßarrestin interaction through modification of either co...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.11.016
更新日期：2011-04-01 00:00:00
abstract：:Modulation of immune responses is an important strategy employed by pathogens to enable their survival in host organisms. Secreted immunomodulatory molecules are key weapons in the pathogen's battle with the host immune system. In this review, we will discuss the immunomodulatory effects of the phosphorylcholine-conta...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2004.05.014
更新日期：2005-01-01 00:00:00
abstract：:Slug, a Snail-related zinc-finger transcription factor implicated in the increased motility of mesenchymal cells during embryonic development and progression of cancer cells towards an invasive phenotype, plays a specific and critical role in the pathogenesis of Bcr-Abl-associated leukemias. Here we report that Slug o...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.04.002
更新日期：2010-08-01 00:00:00
abstract：:Self-renewing divisions of normal and cancerous stem cells are responsible for the initiation and maintenance of normal and certain cancerous tissues, respectively. Recent findings suggest that tumor surveillance mechanisms can reduce regenerative capacity and frequency of normal stem cells, thereby contributing to ti...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2007.06.021
更新日期：2007-12-01 00:00:00
