Obestatin stimulates Akt signalling in gastric cancer cells through beta-arrestin-mediated epidermal growth factor receptor transactivation.

Abstract:

:Obestatin was identified as a gut peptide encoded by the ghrelin gene that interacts with the G protein-coupled receptor, GPR39. In this work, a sequential analysis of its transmembrane signalling pathway has been undertaken to characterize the intracellular mechanisms responsible for Akt activation. The results show that Akt activation requires the phosphorylation of T308 in the A-loop by the phosphoinositide-dependent kinase 1 (PDK1) and S473 within the HM by the mammalian target of rapamycin (mTOR) kinase complex 2 (mTORC2: Rictor, mLST8, mSin1, mTOR kinase) with participation neither of G(i)(/o)-protein nor Gbetagamma dimers. Obestatin induces the association of GPR39/beta-arrestin 1/Src signalling complex resulting in the transactivation of the epidermal growth factor receptor (EGFR) and downstream Akt signalling. Upon administration of obestatin, phosphorylation of mTOR (S2448) and p70S6K1 (T389) rise with a time course that parallels that of Akt activation. Based on the experimental data obtained, a signalling pathway involving a beta-arrestin 1 scaffolding complex and EGFR to activate Akt signalling is proposed.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Alvarez CJ,Lodeiro M,Theodoropoulou M,Camiña JP,Casanueva FF,Pazos Y

doi

10.1677/ERC-08-0192

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

599-611

issue

2

eissn

1351-0088

issn

1479-6821

pii

ERC-08-0192

journal_volume

16

pub_type

杂志文章
  • Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours.

    abstract::Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, well-characterized centre-based patient...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0017

    authors: Pape UF,Berndt U,Müller-Nordhorn J,Böhmig M,Roll S,Koch M,Willich SN,Wiedenmann B

    更新日期:2008-12-01 00:00:00

  • Sporadic hypercalcitoninemia: clinical and therapeutic consequences.

    abstract::'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0059

    authors: Scheuba C,Kaserer K,Moritz A,Drosten R,Vierhapper H,Bieglmayer C,Haas OA,Niederle B

    更新日期:2009-03-01 00:00:00

  • MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma.

    abstract::Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-15-0162

    authors: Romitti M,Wajner SM,Ceolin L,Ferreira CV,Ribeiro RV,Rohenkohl HC,Weber Sde S,Lopez PL,Fuziwara CS,Kimura ET,Maia AL

    更新日期:2016-03-01 00:00:00

  • Overexpression of the natural antisense hypoxia-inducible factor-1alpha transcript is associated with malignant pheochromocytoma/paraganglioma.

    abstract::Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors cha...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-10-0184

    authors: Span PN,Rao JU,Oude Ophuis SB,Lenders JW,Sweep FC,Wesseling P,Kusters B,van Nederveen FH,de Krijger RR,Hermus AR,Timmers HJ

    更新日期:2011-04-28 00:00:00

  • In vitro model systems to study androgen receptor signaling in prostate cancer.

    abstract::Prostate cancer (PCa) is one of the most common causes of male cancer-related death in Western nations. The cellular response to androgens is mediated via the androgen receptor (AR), a ligand-inducible transcription factor whose dysregulation plays a key role during PCa development and progression following androgen d...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-12-0401

    authors: Sampson N,Neuwirt H,Puhr M,Klocker H,Eder IE

    更新日期:2013-03-26 00:00:00

  • Expression and therapeutic relevance of heat-shock protein 90 in pancreatic endocrine tumors.

    abstract::Pancreatic endocrine tumors (PET) represent a heterogenous group of neoplasms. Although surgical resection is considered a safe and effective treatment for many PET, therapeutic options for inoperable and progressive PET are limited. The expression of heat-shock protein (HSP) 90 was investigated in 120 clinically and ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-11-0227

    authors: Mayer P,Harjung A,Breinig M,Fischer L,Ehemann V,Malz M,Scherübl H,Britsch S,Werner J,Kern MA,Bläker H,Schirmacher P,Bergmann F

    更新日期:2012-05-03 00:00:00

  • Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases.

    abstract::This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused by a solid fibrous ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/ERC-07-0161

    authors: de Groot JW,Rikhof B,van Doorn J,Bilo HJ,Alleman MA,Honkoop AH,van der Graaf WT

    更新日期:2007-12-01 00:00:00

  • Mouse models of transforming growth factor beta impact in breast development and cancer.

    abstract::It is now recognized that transforming growth factor beta (TGF-beta) is an important factor that regulates normal breast development as well as breast cancer. Genetically engineered mouse models have been used to determine the role and mechanism of TGF-beta action in normal development and diseases of the breast. Usin...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/erc.1.00936

    authors: Serra R,Crowley MR

    更新日期:2005-12-01 00:00:00

  • Autophagy and thyroid carcinogenesis: genetic and epigenetic links.

    abstract::Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-13-0271

    authors: Morani F,Titone R,Pagano L,Galetto A,Alabiso O,Aimaretti G,Isidoro C

    更新日期:2013-12-16 00:00:00

  • A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping.

    abstract::Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes - potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/mal...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-06-0048

    authors: Fujarewicz K,Jarzab M,Eszlinger M,Krohn K,Paschke R,Oczko-Wojciechowska M,Wiench M,Kukulska A,Jarzab B,Swierniak A

    更新日期:2007-09-01 00:00:00

  • Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies.

    abstract::Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the cont...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0342

    authors: Zamagni C,Wirtz RM,De Iaco P,Rosati M,Veltrup E,Rosati F,Capizzi E,Cacciari N,Alboni C,Bernardi A,Massari F,Quercia S,D'Errico Grigioni A,Dietel M,Sehouli J,Denkert C,Martoni AA

    更新日期:2009-12-01 00:00:00

  • Peroxisome proliferator-activated receptor gamma and BRCA1.

    abstract::Peroxisome proliferator-activated receptor gamma agonists have been proposed as breast cancer preventives. Individuals who carry a mutated copy of BRCA1, DNA repair-associated gene, are at increased risk for development of breast cancer. Published data in the field suggest there could be interactions between peroxisom...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-18-0449

    authors: Furth PA

    更新日期:2019-02-01 00:00:00

  • ATP binding cassette transporters and drug resistance in breast cancer.

    abstract::Resistance to chemotherapy is a critical issue in the management of breast cancer patients. The nature of clinical drug resistance is likely to be multifactorial. However, in the last decade considerable attention has been dedicated to the role played by membrane transporter proteins belonging to the ATP binding casse...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/erc.0.0100043

    authors: Leonessa F,Clarke R

    更新日期:2003-03-01 00:00:00

  • Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma.

    abstract::Numerous epidemiological observations point to sex differences in lung cancer etiology and progression. The present study was aimed at understanding the bases of these sex differences. To test the effect of estradiol on tumor progression, we used a mouse model based on conditional Kras expression and concurrent deleti...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0002

    authors: Hammoud Z,Tan B,Badve S,Bigsby RM

    更新日期:2008-06-01 00:00:00

  • Risks of breast, endometrial, and ovarian cancers after twin births.

    abstract::The concentrations of endogenous hormones differ between women with twin and singleton births, with a possible influence on the risk of cancer. We used the nationwide Swedish Family-Cancer Database, including 30,409 women with a twin birth, to examine the subsequent risks of breast, endometrial, and ovarian cancers. R...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-07-0088

    authors: Ji J,Försti A,Sundquist J,Hemminki K

    更新日期:2007-09-01 00:00:00

  • Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

    abstract::Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,随机对照试验

    doi:10.1530/ERC-12-0229

    authors: Dallal CM,Brinton LA,Bauer DC,Buist DS,Cauley JA,Hue TF,Lacroix A,Tice JA,Chia VM,Falk R,Pfeiffer R,Pollak M,Veenstra TD,Xu X,Lacey JV Jr,B~FIT Research Group.

    更新日期:2013-02-18 00:00:00

  • Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma.

    abstract::Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAFV600E are markers of malignancy useful to improve FNAB accuracy. The objective of this study was to determine whether the combined analysis of Gal-3 and BRAFV600E expression in t...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-07-0147

    authors: Sapio MR,Guerra A,Posca D,Limone PP,Deandrea M,Motta M,Troncone G,Caleo A,Vallefuoco P,Rossi G,Fenzi G,Vitale M

    更新日期:2007-12-01 00:00:00

  • Deubiquitinases and the new therapeutic opportunities offered to cancer.

    abstract::Deubiquitinases (DUBs) play important roles and therefore are potential drug targets in various diseases including cancer and neurodegeneration. In this review, we recapitulate structure-function studies of the most studied DUBs including USP7, USP22, CYLD, UCHL1, BAP1, A20, as well as ataxin 3 and connect them to reg...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-14-0516

    authors: Pfoh R,Lacdao IK,Saridakis V

    更新日期:2015-02-01 00:00:00

  • Genomic classification of benign adrenocortical lesions.

    abstract::Benign adrenal tumors cover a spectrum of lesions with distinct morphology and steroid secretion. Current classification is empirical. Beyond a few driver mutations, pathophysiology is not well understood. Here, a pangenomic characterization of benign adrenocortical tumors is proposed, aiming at unbiased classificatio...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-20-0128

    authors: Faillot S,Foulonneau T,Néou M,Espiard S,Garinet S,Vaczlavik A,Jouinot A,Rondof W,Septier A,Drougat L,Hécale-Perlemoine K,Ragazzon B,Rizk-Rabin M,Sibony M,Bonnet-Serrano F,Guibourdenche J,Libé R,Groussin L,Dousset B,

    更新日期:2021-01-01 00:00:00

  • Annual fasting plasma glucose variation increases risk of cancer incidence and mortality in patients with type 2 diabetes: the Taichung Diabetes Study.

    abstract::The study aims to examine whether the annual variations in fasting plasma glucose (FPG) measurements, represented by the coefficient of variation (CV), predict cancer incidence and mortality in the subsequent years independent of traditional risk factors of type 2 diabetic patients. A computerized database of patients...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-12-0038

    authors: Lin CC,Li CI,Liu CS,Lin WY,Chen CC,Yang SY,Lee CC,Li TC

    更新日期:2012-07-18 00:00:00

  • Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course.

    abstract::The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which s...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-17-0452

    authors: Kaczmarek-Ryś M,Ziemnicka K,Pławski A,Budny B,Michalak M,Hryhorowicz S,Hoppe-Gołębiewska J,Boruń P,Gołąb M,Czetwertyńska M,Sromek M,Szalata M,Ruchała M,Słomski R

    更新日期:2018-04-01 00:00:00

  • Tetrac as an anti-angiogenic agent in cancer.

    abstract::The thyroid hormones T3 and T4 have emerged as pro-angiogenic hormones with important implications for cancer management. Endogenous circulating hormone levels may help stimulate cancer progression and limit the effectiveness of anticancer therapy, though clinical data remain inconclusive. The capacity of thyroid horm...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-19-0058

    authors: Schmohl KA,Nelson PJ,Spitzweg C

    更新日期:2019-06-01 00:00:00

  • The oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium.

    abstract::Cancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxy...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-07-0008

    authors: Kato S,Sadarangani A,Lange S,Villalón M,Brañes J,Brosens JJ,Owen GI,Cuello M

    更新日期:2007-06-01 00:00:00

  • Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer.

    abstract::The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 p...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.1.01216

    authors: Generali D,Fox SB,Berruti A,Brizzi MP,Campo L,Bonardi S,Wigfield SM,Bruzzi P,Bersiga A,Allevi G,Milani M,Aguggini S,Dogliotti L,Bottini A,Harris AL

    更新日期:2006-09-01 00:00:00

  • The ubiquitin-proteasome system: opportunities for therapeutic intervention in solid tumors.

    abstract::The destruction of proteins via the ubiquitin-proteasome system is a multi-step, complex process involving polyubiquitination of substrate proteins, followed by proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors of the proteasome promote the accumulation of proteins that are deleterious t...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-14-0005

    authors: Johnson DE

    更新日期:2015-02-01 00:00:00

  • mTOR inhibition, a potential novel approach for bronchial carcinoids.

    abstract::Although targeted therapy, including inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, being developed for carcinoids arised from the gastrointestinal tract, treatment for locally advanced or metastatic bronchial carcinoids (BCs) remains lacking. Traditional cytotoxic chemother...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-10-0290

    authors: Dong M,Yao JC

    更新日期:2011-04-28 00:00:00

  • Obesity and menopause modify the epigenomic profile of breast cancer.

    abstract::Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-16-0565

    authors: Crujeiras AB,Diaz-Lagares A,Stefansson OA,Macias-Gonzalez M,Sandoval J,Cueva J,Lopez-Lopez R,Moran S,Jonasson JG,Tryggvadottir L,Olafsdottir E,Tinahones FJ,Carreira MC,Casanueva FF,Esteller M

    更新日期:2017-07-01 00:00:00

  • A novel role of Shc adaptor proteins in steroid hormone-regulated cancers.

    abstract::Tyrosine phosphorylation plays a critical role in growth regulation, and its aberrant regulation can be involved in carcinogenesis. The association of Shc (Src homolog and collagen homolog) adaptor protein family members in tyrosine phosphorylation signaling pathway is well recognized. Shc adaptor proteins transmit ac...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/ERC-08-0179

    authors: Alam SM,Rajendran M,Ouyang S,Veeramani S,Zhang L,Lin MF

    更新日期:2009-03-01 00:00:00

  • Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer.

    abstract::The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over hal...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-17-0014

    authors: Lam AK,Saremi N

    更新日期:2017-04-01 00:00:00

  • Role of exon-16-deleted HER2 in breast carcinomas.

    abstract::A splice variant of the human gene HER2, lacking exon-16 (DeltaHER2) which encodes a small extracellular region, has been described. This altered receptor forms disulfide bond-stabilized homodimers. We report here that the DeltaHER2 splice variant represents about 9% of the HER2 mRNA obtained from most of the 46 breas...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.1.01047

    authors: Castiglioni F,Tagliabue E,Campiglio M,Pupa SM,Balsari A,Ménard S

    更新日期:2006-03-01 00:00:00