当前位置： SCI文献检索 > Translational Oncology期刊下所有文献 > Loss of PI(4,5)P2 5-Phosphatase A Contributes to Resistance of Human Melanoma Cells to RAF/MEK Inhibitors.

Loss of PI(4,5)P2 5-Phosphatase A Contributes to Resistance of Human Melanoma Cells to RAF/MEK Inhibitors.

Abstract：

:Past studies have shown that the inositol polyphosphate 5-phosphatase, phosphatidylinositol 4,5-bisphosphate 5-phosphatase (PIB5PA), is commonly downregulated or lost in melanomas, which contributes to elevated activation of phosphatidylinositol 3-kinase (PI3K)/Akt in melanoma cells. In this report, we provide evidence that PIB5PA deficiency plays a role in resistance of melanoma cells to RAF/mitogen-activated protein kinase kinase (MEK) inhibitors. Ectopic expression of PIB5PA enhanced apoptosis induced by the RAF inhibitor PLX4720 in BRAF(V600E) and by the MEK inhibitor U0126 in both BRAF(V600E) and wild-type BRAF melanoma cells. This was due to inhibition of PI3K/Akt, as co-introduction of an active form of Akt (myr-Akt) abolished the effect of overexpression of PIB5PA on apoptosis induced by PLX4720 or U0126. While overexpression of PIB5PA triggered activation of Bad and down-regulation of Mcl-1, knockdown of Bad or overexpression of Mcl-1 recapitulated, at least in part, the effect of myr-Akt, suggesting that regulation of Bad and Mcl-1 is involved in PIB5PA-mediated sensitization of melanoma cells to the inhibitors. The role of PIB5PA deficiency in BRAF inhibitor resistance was confirmed by knockdown of PIB5PA, which led to increased growth of BRAF(V600E) melanoma cells selected for resistance to PLX4720. Consistent with its role in vitro, overexpression of PIB5PA and the MEK inhibitor selumetinib cooperatively inhibited melanoma tumor growth in a xenograft model. Taken together, these results identify loss of PIB5PA as a novel resistance mechanism of melanoma to RAF/MEK inhibitors and suggest that restoration of PIB5PA may be a useful strategy to improve the therapeutic efficacy of the inhibitors in the treatment of melanoma.

journal_name

Transl Oncol

journal_title

Translational oncology

authors

Ye Y,Li Q,Hu WL,Tseng HY,Jin L,Zhang XD,Zhang LJ,Yang S

doi

10.1593/tlo.13277

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

470-81

issue

4

issn

1936-5233

journal_volume

6

pub_type

杂志文章

相关文献

Translational Oncology文献大全
  • Altered microRNA Expression Patterns in Hepatoblastoma Patients.

    abstract：:Liver cancers in children are rare representing only 1.1% of malignancies, with an annual incidence rate of 1.5 cases per million. Hepatoblastoma and hepatocellular carcinomas are the most common malignancies of the liver occurring in young people aged 15 years or younger. Molecular basis of both tumors are still uncl...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.09124

    authors： Magrelli A,Azzalin G,Salvatore M,Viganotti M,Tosto F,Colombo T,Devito R,Di Masi A,Antoccia A,Lorenzetti S,Maranghi F,Mantovani A,Tanzarella C,Macino G,Taruscio D

    更新日期：2009-08-18 00:00:00

  • Activation Status of Receptor Tyrosine Kinases as an Early Predictive Marker of Response to Chemotherapy in Osteosarcoma.

    abstract：:Receptor tyrosine kinases (RTKs) are membrane receptors that play a vital role in various biological processes, in particular, cell survival, cell proliferation, and cell differentiation. These cellular processes are composed of multitiered signaling cascades of kinases starting from ligand binding to extracellular do...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2017.08.005

    authors： Chaiyawat P,Klangjorhor J,Settakorn J,Champattanachai V,Phanphaisarn A,Teeyakasem P,Svasti J,Pruksakorn D

    更新日期：2017-10-01 00:00:00

  • Inhibitor of DNA Binding 2 Inhibits Epithelial-Mesenchymal Transition via Up-Regulation of Notch3 in Breast Cancer.

    abstract：:Breast cancer is the second leading cause of cancer death in women worldwide. Incurable metastatic breast disease presents a major clinical challenge and is the main cause of breast cancer-related death. The epithelial-mesenchymal transition (EMT) is a critical early promoter of metastasis. In the present study, we id...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2018.07.015

    authors： Wen XF,Chen M,Wu Y,Chen MN,Glogowska A,Klonisch T,Zhang GJ

    更新日期：2018-10-01 00:00:00

  • Combined Selection System to Lower the Cutoff for Plasma Cell Enrichment Applied to iFISH Analysis in Multiple Myeloma.

    abstract：:Multiple myeloma (MM) is a very heterogeneous disease, characterized by multiple cytogenetic aberrations on plasma cells (PC) that have been traditionally used to predict the outcome of the disease. A mayor issue on the analysis of PC is the sometimes low infiltration of these cells in the bone marrow that hampers cyt...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2018.02.021

    authors： Mansilla C,Soria E,Vallejo M,Valiente A,Perez-Juana A,Zabalza A,Hurtado G,Sala F,Ramírez N

    更新日期：2018-06-01 00:00:00

  • The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non-Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy.

    abstract：:The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemot...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2016.09.006

    authors： Jia M,Xu Y,Zhu M,Wang M,Sun M,Qian J,Chang J,Wei Q

    更新日期：2016-12-01 00:00:00

  • Acquired Uniparental Disomy Regions Are Associated with Disease Outcome in Patients with Oral Cavity and Oropharynx But Not Larynx Cancers.

    abstract：:Acquired uniparental disomy (aUPD) regions pinpoint homozygousity and monoallelic expressed genes. We analyzed The Cancer Genome Atlas single-nucleotide polymorphism arrays and expression data from oral cavity, oropharynx, and larynx cancers to identify frequency of aUPD in each tumor type and association of aUPD regi...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2020.100763

    authors： Tuna M,I Amos C,B Mills G

    更新日期：2020-05-01 00:00:00

  • Glucose metabolism measured by [¹⁸F]fluorodeoxyglucose positron emission tomography is independent of PTEN/AKT status in human colon carcinoma cells.

    abstract：:The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most altered in cancer, leading to a range of cellular responses including enhanced proliferation, survival, and metabolism, and is thus an attractive target for anticancer drug development. Stimulation of the PI3K pathway can be initiated by alterat...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.11118

    authors： Nguyen QD,Perumal M,Waldman TA,Aboagye EO

    更新日期：2011-08-01 00:00:00

  • Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer.

    abstract：:We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and ...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2017.03.008

    authors： Bhosale PG,Cristea S,Ambatipudi S,Desai RS,Kumar R,Patil A,Kane S,Borges AM,Schäffer AA,Beerenwinkel N,Mahimkar MB

    更新日期：2017-06-01 00:00:00

  • Spatiotemporal Optoacoustic Mapping of Tumor Hemodynamics in a Clinically Relevant Orthotopic Rabbit Model of Head and Neck Cancer.

    abstract：:The purpose of this study was to investigate the usefulness of photoacoustic imaging (PAI) for spatiotemporal mapping of tumor hemodynamics in a rabbit model of head and neck carcinoma. Shope cottontail rabbit papilloma virus associated VX2 carcinomas were established in adult male New Zealand White rabbits (n = 9) by...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2017.08.004

    authors： Rich LJ,Sexton S,Curtin L,Seshadri M

    更新日期：2017-10-01 00:00:00

  • Control of Glycolytic Flux by AMP-Activated Protein Kinase in Tumor Cells Adapted to Low pH.

    abstract：:Tumor cells grow in nutrient- and oxygen-deprived microenvironments and adapt to the suboptimal growth conditions by altering their metabolic pathways. This adaptation process commonly results in a tumor phenotype that displays a high rate of aerobic glycolysis and aggressive tumor characteristics. The glucose regulat...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.11319

    authors： Mendoza EE,Pocceschi MG,Kong X,Leeper DB,Caro J,Limesand KH,Burd R

    更新日期：2012-06-01 00:00:00

  • Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma.

    abstract：:Fasting reduces gastrointestinal cellular proliferation rates through G1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effec...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2014.04.014

    authors： Withers SS,Kass PH,Rodriguez CO Jr,Skorupski KA,O'Brien D,Guerrero TA,Sein KD,Rebhun RB

    更新日期：2014-05-12 00:00:00

  • Thioredoxin Reductase 1 Expression and Castration-recurrent Growth of Prostate Cancer.

    abstract：INTRODUCTION:Many genes are differentially expressed between androgen-dependent and androgen-independent prostate cancer (CaP). Differential expression analysis and subtractive hybridization previously identified nine genes expressed in intact mice bearing CWR22 tumors and castrated mice bearing recurrent CWR22 tumors ...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.08145

    authors： Singh SS,Li Y,Ford OH,Wrzosek CS,Mehedint DC,Titus MA,Mohler JL

    更新日期：2008-09-01 00:00:00

  • CHFR: A Novel Mitotic Checkpoint Protein and Regulator of Tumorigenesis.

    abstract：:Checkpoint with FHA and RING finger domains (CHFR) was first recognized as an early mitotic checkpoint protein that delayed the cell cycle in response to microtubule-targeting drugs. It is an E3 ubiquitin ligase that ubiquitinates target proteins to direct them to the proteasome for degradation or to alter their activ...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.08109

    authors： Privette LM,Petty EM

    更新日期：2008-07-01 00:00:00

  • Phase I trial of radiotherapy concurrent with twice-weekly gemcitabine for head and neck cancer: translation from preclinical investigations aiming to improve the therapeutic ratio.

    abstract：BACKGROUND:Once-weekly gemcitabine concurrent with radiotherapy was highly effective in the treatment of head and neck cancer (HNC) but limited by high mucosal toxicity. Pre-clinical investigations suggested that delivering gemcitabine at substantially lower doses twice weekly during radiotherapy improved the therapeut...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2014.04.016

    authors： Popovtzer A,Normolle D,Worden FP,Prince ME,Chepeha DB,Wolf GT,Bradford CR,Lawrence TS,Eisbruch A

    更新日期：2014-08-01 00:00:00

  • Smoking-Induced SLPI Expression Hinders HPV Infections Also in Squamous Cell Carcinomas of the Vulva.

    abstract：:In HNSCC, protein- and mRNA-expression of the antileukoproteinase SLPI are significantly inverse correlated with HPV-infection suggesting that elevated expression of SLPI protects against HPV-infections. Moreover, SLPI-expression is up-regulated in HNSCC-patients reporting a smoking habit. Here, we investigate the des...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2018.09.004

    authors： Quabius ES,Loehr J,Haaser D,Günther V,Maass N,Röcken C,Mathiak M,Alkatout I,Hoffmann M

    更新日期：2019-01-01 00:00:00

  • Cyclin-Dependent Kinase 2 Promotes Tumor Proliferation and Induces Radio Resistance in Glioblastoma.

    abstract：:Accumulating evidence indicates that CDK2 promotes hyperproliferation and is associated to poor prognosis in multiple cancer cells. However, the physiological role of CDK2 in GBM and the biological mechanism still remains unclear. In this study, we identified that CDK2 expression was significantly enriched in GBM tumo...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2016.08.007

    authors： Wang J,Yang T,Xu G,Liu H,Ren C,Xie W,Wang M

    更新日期：2016-12-01 00:00:00

  • Reproducibility and Prognosis of Quantitative Features Extracted from CT Images.

    abstract：:We study the reproducibility of quantitative imaging features that are used to describe tumor shape, size, and texture from computed tomography (CT) scans of non-small cell lung cancer (NSCLC). CT images are dependent on various scanning factors. We focus on characterizing image features that are reproducible in the p...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.13844

    authors： Balagurunathan Y,Gu Y,Wang H,Kumar V,Grove O,Hawkins S,Kim J,Goldgof DB,Hall LO,Gatenby RA,Gillies RJ

    更新日期：2014-02-01 00:00:00

  • Dissecting the Biological Heterogeneity within Hormone Receptor Positive HER2 Negative Breast Cancer by Gene Expression Markers Identifies Indolent Tumors within Late Stage Disease.

    abstract：:Hormone receptor positive (HR+) breast cancers are a heterogeneous class with differential prognosis. Although more than half of Indian women present with advanced disease, many such patients do well. We have attempted identification of biologically indolent tumors within HR+HER2- tumors based on gene expression using...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2017.04.011

    authors： Prabhu JS,Korlimarla A,Anupama CE,Alexander A,Raghavan R,Kaul R,Desai K,Rajarajan S,Manjunath S,Correa M,Raman R,Kalamdani A,Prasad M,Patil S,Gopinath KS,Srinath BS,Sridhar TS

    更新日期：2017-08-01 00:00:00

  • Preoperative D-dimer and Gamma-Glutamyltranspeptidase Predict Major Complications and Survival in Colorectal Liver Metastases Patients After Resection.

    abstract：OBJECTIVES:To investigate the predictive value of the pre-operative D-dimer and gamma-glutamyltranspeptidase (GGT) for the prognosis in colorectal liver metastases (CRLM) patients after hepatic resection. METHODS:Two hundred and ninety-two patients between December 2008 and December 2016 and 101 patients at our center...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2019.04.011

    authors： Chen Q,Zhao H,Wu J,Cai J,Li C,Zhao J,Bi X,Li Z,Huang Z,Zhang Y,Cui W,Zhou J

    更新日期：2019-07-01 00:00:00

  • Evaluation of potentially predictive markers for anti-angiogenic therapy with sunitinib in recurrent ovarian cancer patients.

    abstract：INTRODUCTION:In ovarian cancer, new therapeutic strategies are needed because the vast majority of patients develop a recurrence and resistance to platinum derivates. Attached to the AGO-OVAR2.11 study investigating the multityrosine kinase inhibitor sunitinib in recurrent platinum refractory ovarian cancers, this tran...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.13205

    authors： Bauerschlag DO,Hilpert F,Meier W,Rau J,Meinhold-Heerlein I,Maass N,Dubois A,Sehouli J,Arnold N,Schem C,Oberg HH,Baumann K

    更新日期：2013-06-01 00:00:00

  • Interpretation of changes in circulating tumor cell counts.

    abstract：:The presence of circulating tumor cells (CTCs) in the blood of cancer patients may guide the use of therapy. We investigated how to evaluate a reduction in the number of CTCs after administration of therapy. CTCs were enumerated with the CellSearch system in 111 metastatic breast and 185 metastatic prostate cancer pat...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.12247

    authors： Coumans FA,Ligthart ST,Terstappen LW

    更新日期：2012-12-01 00:00:00

  • Markers of Mitochondrial Metabolism in Tumor Hypoxia, Systemic Inflammation, and Adverse Outcome of Rectal Cancer.

    abstract：:Tumor hypoxia contributes to therapy resistance and metastatic progression of locally advanced rectal cancer (LARC). We postulated that the tumor mitochondrial metabolism, manifested by reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) damage, reflects how hypoxic conditions connect to cancer-induced systemi...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2018.09.010

    authors： Bousquet PA,Meltzer S,Sønstevold L,Esbensen Y,Dueland S,Flatmark K,Sitter B,Bathen TF,Seierstad T,Redalen KR,Eide L,Ree AH

    更新日期：2019-01-01 00:00:00

  • Enzastaurin, an inhibitor of PKCbeta, Enhances Antiangiogenic Effects and Cytotoxicity of Radiation against Endothelial Cells.

    abstract：PURPOSE:Angiogenesis plays an important role in pancreas cancer pathobiology. Pancreatic tumor cells secrete vascular endothelial growth factor (VEGF), activating endothelial cell protein kinase C beta (PKCbeta) that phosphorylates GSK3beta to suppress apoptosis and promote endothelial cell proliferation and microvesse...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.08151

    authors： Spalding AC,Zeitlin BD,Wilder-Romans K,Davis ME,Nor JE,Lawrence TS,Ben-Josef E

    更新日期：2008-12-01 00:00:00

  • Prognosis of Glioblastoma With Oligodendroglioma Component is Associated With the IDH1 Mutation and MGMT Methylation Status.

    abstract：:Glioblastoma (GBM) with oligodendroglioma component (GBMO) is a newly described GBM subtype in the 2007 World Health Organization classification. However, its biological and genetic characteristics are largely unknown. We investigated the clinicopathological and molecular features of 34 GBMOs and compared the survival...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2014.10.002

    authors： Myung JK,Cho HJ,Kim H,Park CK,Lee SH,Choi SH,Park P,Yoon JM,Park SH

    更新日期：2014-12-01 00:00:00

  • Decreased skp2 expression is necessary but not sufficient for therapy-induced senescence in prostate cancer.

    abstract：:Therapy-induced senescence (TIS), a cytostatic stress response in cancer cells, is induced inefficiently by current anticancer agents and radiation. The mechanisms that mediate TIS in cancer cells are not well defined. Herein, we characterize a robust senescence response both in vitro and in vivo to the quinone diaziq...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.12181

    authors： Ewald JA,Jarrard DF

    更新日期：2012-08-01 00:00:00

  • Selecting Potential Targetable Biomarkers for Imaging Purposes in Colorectal Cancer Using TArget Selection Criteria (TASC): A Novel Target Identification Tool.

    abstract：:Peritoneal carcinomatosis (PC) of colorectal origin is associated with a poor prognosis. However, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is available for a selected group of PC patients, which significantly increases overall survival rates up to 30%. As a consequence, there is su...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1593/tlo.10220

    authors： van Oosten M,Crane LM,Bart J,van Leeuwen FW,van Dam GM

    更新日期：2011-04-01 00:00:00

  • Prognosis of primary hepatic lymphoma: A US population-based analysis.

    abstract：OBJECTIVE:Primary hepatic lymphoma (PHL) is a rare malignancy with lesions confined to the liver. It is characterized by a large number of monomorphic, medium-sized lymphocytic infiltrates in the hepatic sinusoid. Due to the rarity of this malignancy, our current understanding of PHL is limited. METHODS:We collected i...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2020.100931

    authors： Qiu MJ,Fang XF,Huang ZZ,Li QT,Wang MM,Jiang X,Xiong ZF,Yang SL

    更新日期：2021-01-01 00:00:00

  • Absent in melanoma 2-mediating M1 macrophages facilitate tumor rejection in renal carcinoma.

    abstract：:Absent in melanoma 2 (AIM2) as an immune regulator for the regulation of tumor-associated macrophages (TAMs) function is unclear in tumor development. Here, the AIM2 function was investigated in TAMs-mediated malignant behaviors of renal carcinoma. The correlation analysis result showed that the AIM2 expression in TAM...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2021.101018

    authors： Chai D,Zhang Z,Shi SY,Qiu D,Zhang C,Wang G,Fang L,Li H,Tian H,Li H,Zheng J

    更新日期：2021-01-22 00:00:00

  • Pathological Pattern of Intrahepatic HBV in HCC is Phenocopied by PDX-Derived Mice: a Novel Model for Antiviral Treatment.

    abstract：BACKGROUND:Hepatitis B virus (HBV) is one of the most prominent risk factors for hepatocellular carcinoma (HCC) development and virus-mediated cases represents more than 80% of HCC in East Asia, where it is endemic. Currently, the HBV status of pathological HCC is not fully clarified, especially by comparison to nontum...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2019.05.006

    authors： Liu J,Chen S,Zou Z,Tan D,Liu X,Wang X

    更新日期：2019-09-01 00:00:00

  • Relative expression of KLK5 to LEKTI is associated with aggressiveness of oral squamous cell carcinoma.

    abstract：BACKGROUND:Oral squamous cell carcinoma (OSCC) remains a challenging cancer to treat despite all the advances of the last 50 years. Kallikrein 5 (KLK5) is among the serine proteases implicated in OSCC development. However, whether the activity of KLK5 promotes carcinogenesis is still controversial. Moreover, knowledge ...

    journal_title：Translational oncology

    pub_type： 杂志文章

    doi：10.1016/j.tranon.2020.100970

    authors： Alves MG,Kodama MH,da Silva EZM,Gomes BBM,da Silva RAA,Vieira GV,Alves VM,da Fonseca CK,Santana AC,Cecílio NT,Costa MSA,Jamur MC,Oliver C,Cunha TM,Bugge TH,Braz-Silva PH,Colli LM,Sales KU

    更新日期：2021-01-01 00:00:00