Abstract:
:The rational making the G protein-coupled receptors (GPCR) the centerpiece of targeted therapies is fueled by the awareness that GPCR-initiated signaling acts as pivotal driver of the early stages of progression in a broad landscape of human malignancies. The endothelin-1 (ET-1) receptors (ET-1R), known as ETA receptor (ETAR) and ETB receptor (ETBR) that belong to the GPCR superfamily, affect both cancer initiation and progression in a variety of cancer types. By the cross-talking with multiple signaling pathways mainly through the scaffold protein β-arrestin1 (β-arr1), ET-1R axis cooperates with an array of molecular determinants, including transcription factors and co-factors, strongly affecting tumor cell fate and behavior. In this scenario, recent findings shed light on the interplay between ET-1 and the Hippo pathway. In ETAR highly expressing tumors ET-1 axis induces the de-phosphorylation and nuclear accumulation of the Hippo pathway downstream effectors, the paralogous transcriptional cofactors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). Recent evidence have discovered that ET-1R/β-arr1 axis instigates a transcriptional interplay involving YAP and mutant p53 proteins, which share a common gene signature and cooperate in a oncogenic signaling network. Mechanistically, YAP and mutp53 are enrolled in nuclear complexes that turn on a highly selective YAP/mutp53-dependent transcriptional response. Notably, ET-1R blockade by the FDA approved dual ET-1 receptor antagonist macitentan interferes with ET-1R/YAP/mutp53 signaling interplay, through the simultaneous suppression of YAP and mutp53 functions, hampering metastasis and therapy resistance. Based on these evidences, we aim to review the recent findings linking the GPCR signaling, as for ET-1R, to YAP/TAZ signaling, underlining the clinical relevance of the blockade of such signaling network in the tumor and microenvironmental contexts. In particular, we debate the clinical implications regarding the use of dual ET-1R antagonists to blunt gain of function activity of mutant p53 proteins and thereby considering them as a potential therapeutic option for mutant p53 cancers. The identification of ET-1R/β-arr1-intertwined and bi-directional signaling pathways as targetable vulnerabilities, may open new therapeutic approaches able to disable the ET-1R-orchestrated YAP/mutp53 signaling network in both tumor and stromal cells and concurrently sensitizes to high-efficacy combined therapeutics.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Tocci P,Blandino G,Bagnato Adoi
10.1186/s13046-021-01827-8subject
Has Abstractpub_date
2021-01-09 00:00:00pages
27issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-021-01827-8journal_volume
40pub_type
杂志文章,评审abstract:BACKGROUND:Recently, leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a negative regulator of EGFR, was discovered is a novel agent for suppressing bladder cancer. The aim of this study was to investigate the impact of LRIG1 on the biological features of aggressive bladder cancer cells and the possible m...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-32-101
更新日期:2013-12-08 00:00:00
abstract::Increased expression of CD44 variants is often observed in differentiated thyroid carcinomas. To establish a method for gene diagnosis of thyroid without any additional invasions to the patients, RNA in leftover cells inside the needle used for fine needle aspiration biopsies (FNABs) was extracted to detect the expres...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:Cancer stem cells (CSCs) are important in the tumorigenesis and progression of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play crucial roles regulating CD133+ and EpCAM+ CSCs in HCC, although it is unclear whether miRNAs regulate CD90+ CSCs in HCC. METHODS:The miRNA profiles of CD90+ and CD90- HCC c...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0452-6
更新日期:2016-11-11 00:00:00
abstract:BACKGROUND:Enzymatically inactive chitinase-like protein CHI3L1 drives inflammatory response and promotes tumor progression. However, its role in gastric cancer (GC) tumorigenesis and metastasis has not yet been fully elucidated. We determined the significance of CHI3L1 expression in patients with GC. We also explored ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0876-2
更新日期:2018-08-30 00:00:00
abstract:BACKGROUND:Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a gene family involved in multiple malignancies. CMTM4 is a member of this family and is located at chromosome 16q22.1, a locus that harbours a number of tumour suppressor genes. It has been defined as a regulator of ce...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0236-4
更新日期:2015-10-16 00:00:00
abstract::We evaluated the effect of interferon-alpha2b as a chemosensitiser on HCT-15 cell line in treatment with doxorubicin. Chemosensitivity was determined by [3H]-thymidine incorporation and tetrazolium assays. The levels of expression of P-glycoprotein, Bcl-2 oncoprotein and HLA-ABC complex, and cell cycle/apoptosis analy...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of tumors, with aggressive clinical course that renders prognostication and choice of treatment strategy difficult. Chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is the current first-line trea...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0768-5
更新日期:2018-05-02 00:00:00
abstract:PURPOSE:To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. METHODS:A meta-analysis of randomized controlled trials (RCT)...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,meta分析
doi:10.1186/1756-9966-28-1
更新日期:2009-01-06 00:00:00
abstract:BACKGROUND:Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have bee...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-40
更新日期:2011-04-13 00:00:00
abstract::Radiofrequency Thermal Ablation (RFA) of liver tumors is done by percutaneous, laparoscopic and open surgical approach. Selection criteria for percutaneous or open surgical ablation of 65 hepatic lesions are here evaluated in 45 patients treated in a two-years period. Twenty-five patients were males and 20 females, ag...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:This study was conducted to investigate the expression of CXCR4 in portal vein tumor thrombus (PVTT) tissue and its possible role in the invasiveness of tumor thrombus cells. METHODS:We detected differential expression of CXCR4 between PVTT and hepatocellular carcinoma (HCC) by an immunohistochemical assay....
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-156
更新日期:2010-11-27 00:00:00
abstract::We measured the serum level of soluble Fas (sFas) antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients to investigate immune response of B lymphoma cells in gastric MALT lymphoma. The serum sFas antigen levels in 21 patients with Helicobacter pylori (HP)-positive MALT lymphoma were 4.51+/-0.25...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB d...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/1756-9966-30-115
更新日期:2011-12-29 00:00:00
abstract::Escherichia coli cytosine deaminase (CD), which is a prokaryotic enzyme, converts nontoxic prodrug 5-fluorocytosine (5-FC) into the toxic chemotherapeutic agent 5-fluorouracil (5-FU). To investigate an enzyme/prodrug gene therapy for colorectal cancer, using adenoviral gene transfer of the E. coli CD gene associated w...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Cancer-associated fibroblasts (CAFs) plays an essential role in cancer cell growth, metabolism and immunoreaction. Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. Targeting autophagy has gained interest with multiple preclinical and clinical tri...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1172-5
更新日期:2019-04-23 00:00:00
abstract::Primary cancer of the gallbladder is not unusual. Most cases of gallbladder cancer are found at an advanced stage, accompanied by the invasion to the liver, metastases to the lymph nodes and distant organs, and peritoneal dissemination. In this study, we first examined the effect of mitogen-activated protein kinase ki...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly developed countries. Radiotherapy plays a critical role in the curative management of inoperable non-small cell lung cancer (NSCLC) and is also used as a post-surgical treatment in lung cancer patients....
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0285-3
更新日期:2016-01-12 00:00:00
abstract:BACKGROUND:The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, d...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-021-01841-w
更新日期:2021-01-23 00:00:00
abstract::In the deletion mapping of chromosome (chr) 9 in head and neck lesions of the Indian patient population by microsatellite markers, we have identified four discrete areas (D1-D4) with high loss of heterozygosities (LOHs) viz. 9p24-p23 (D1), 9p22-p21 (D2), 9q11-q13 (D3) and 9q22.3 (D4) regions. The deletions in D2 and D...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 历史文章,杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND:Dysregulated endocytosis of membrane proteins contributes significantly to several hallmarks of cancer. Basigin can enhance cancer progression, but its precise mechanism remains unclear. CD98 promotes cell spreading and tumorigenicity by triggering integrin clustering and enhancing cell adhesion to the extra...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0226-6
更新日期:2015-10-06 00:00:00
abstract::The heterogeneous tumor microenvironment (TME) is highly complex and not entirely understood. These complex configurations lead to the generation of oxygen-deprived conditions within the tumor niche, which modulate several intrinsic TME elements to promote immunosuppressive outcomes. Decoding these communications is n...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-020-01583-1
更新日期:2020-05-01 00:00:00
abstract::Adenosquamous carcinomas of the colorectum are rare neoplasms. Our experience with two cases is presented in this paper. One patient, who complained of bloody stool, was found to have adenocarcinoma in the sigmoid colon. He received a laparoscopy-assisted sigmoidectomy. The histological examination revealed that the t...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND:Hepatoblastoma (HB) is a common liver malignancy in children. Our previous study has disclosed the crucial role of STAT3 (signal transducer and activator of transcription 3) in HB. AIM OF THE STUDY:Present study was designed to study the circular RNA (circRNA) STAT3 in HB. METHODS:Gel electrophoresis revea...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01598-8
更新日期:2020-06-03 00:00:00
abstract:BACKGROUND:Gastric cancer remains a major cause of mortality and morbidity worldwide. In recent years, gene-based therapeutic strategies were confirmed promising in cancer inhibition and attracted great attention. RNA interference (RNAi) is a powerful tool for gene therapy and has been widely employed to aid in treatme...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0334-y
更新日期:2016-03-31 00:00:00
abstract::Here we report the case of a patient with a soft tissue mass of the neck. For more than 10 years it was thought to be a branchial cyst and was later diagnosed to be a cystic lymph node metastasis from an occult thyroid carcinoma. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::Telomeres, the nucleoprotein structures that cap the ends of eukaryotic chromosomes, play important and multiple roles in tumorigenesis. Functional telomeres need the establishment of a protective chromatin structure based on the interplay between the specific complex named shelterin and a tight nucleosomal organizati...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1030-5
更新日期:2019-01-17 00:00:00
abstract:INTRODUCTION:Women with ductal hyperplasia including usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH) have an increased risk of developing invasive ductal carcinoma (IDC) of breast. The importance of several molecular markers in breast cancer has been of considerable interest during recent years suc...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-112
更新日期:2010-08-16 00:00:00
abstract:BACKGROUND:Ovarian cancer (OC) is the most lethal gynecological malignancy and the second leading cause of cancer-related death in women. Treatment with PARP inhibitors (PARPi), such as Olaparib, has been recently introduced for OC patients, but resistance may occur and underlying mechanisms are still poorly understood...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1490-7
更新日期:2020-01-02 00:00:00
abstract:BACKGROUND:Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The fu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01704-w
更新日期:2020-10-28 00:00:00
abstract:BACKGROUND:Tumour-associated macrophages (TAMs) in the tumour microenvironment (TME) can promote the progression of hepatocellular carcinoma (HCC). Some tumours can be suppressed by targeting Wnt2b in tumour cells. However, the role of Wnt2b in HCC is still unknown. In particular, the role of Wnt2b-mediated signal acti...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01808-3
更新日期:2021-01-06 00:00:00