Abstract:
:Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been demonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples and cell lines, down-regulates the expression of PD-L1, an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T-cells. Our data suggests that this novel mechanism of PD-L1 regulation is mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Additionally, we observed that selective HDAC6 inhibitors impairs tumor growth and reduce the in vivo expression of several inhibitory check-point molecules and other regulatory pathways involved in immunosurveillance. Most importantly, these results provide a key pre-clinical rationale and justification to further study isotype selective HDAC6 inhibitors as potential immuno-modulatory agents in cancer.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
M L,P PV,T K,M P,E S,J P,K V W,C L,F C,S D,M SKS,M M,A K,J PI,A S,E S,J W,E M S,A Vdoi
10.1016/j.molonc.2015.12.012subject
Has Abstractpub_date
2016-05-01 00:00:00pages
735-750issue
5eissn
1574-7891issn
1878-0261journal_volume
10pub_type
杂志文章abstract::A significant proportion of estrogen receptor-positive (ER+) breast cancer (BC) initially responds to endocrine therapy but eventually evolves into therapy-resistant BC. Transcription factor AP-2 gamma (TFAP2C) is a known regulator of ER activity, and high expression of TFAP2C is associated with a decreased response t...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12871
更新日期:2020-12-02 00:00:00
abstract::Glycosylation is the stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process have been associated with malignant transformation. Simultaneous analysis of the expression of all glycan-related genes clearly gives the advantage of enabling a comprehensive...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.12.001
更新日期:2010-04-01 00:00:00
abstract::Breast cancers with BRCA1 germline mutation have a characteristic DNA copy number (CN) pattern. We developed a test that assigns CN profiles to be 'BRCA1-like' or 'non-BRCA1-like', which refers to resembling a BRCA1-mutated tumor or resembling a tumor without a BRCA1 mutation, respectively. Approximately one third of ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.03.002
更新日期:2015-08-01 00:00:00
abstract::The small heat-shock protein of 27 kDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumour behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted ca...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12042
更新日期:2017-06-01 00:00:00
abstract::As a critical feature of the tumor microenvironment, hypoxia is known to be a potent inducer of tumor metastasis, and it has been proposed that the initial steps in metastasis involve epithelial-mesenchymal transition (EMT). The strong correlation among hypoxia, EMT, and metastasis suggests that integrative assessment...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12491
更新日期:2019-07-01 00:00:00
abstract::Chimeric inhibitors, which merge two drug pharmacophores in a single molecule have become a prominent approach for the design of novel anticancer compounds. Here, we examined animacroxam, which combines histone deacetylase (HDAC) inhibitory and cytoskeleton-interfering pharmacophores, in testicular germ cell tumors (T...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12582
更新日期:2019-12-01 00:00:00
abstract::Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from larg...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.04.011
更新日期:2010-06-01 00:00:00
abstract::Endocytosis is an important regulator of cell-cell signaling and endocytic trafficking has been increasingly implicated in control of tumor suppression. Recent insights from Drosophila indicate that impairment of multiple trafficking steps which lead to receptor degradation can cause tumor formation in epithelial orga...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is marked by an abundant stromal deposition. This stroma is suspected to harbor both tumor-promoting and tumor-suppressing properties. This is underscored by the disappointing results of stroma targeting in clinical studies. Given the complexity of tumor-stroma interaction in PD...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12073
更新日期:2017-08-01 00:00:00
abstract::Transient receptor potential melastatin-4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patient...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12566
更新日期:2019-11-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer for which there are no effective therapies. Deep sequencing of PDAC tumors has revealed the presence of a high number of mutations (>50) that affect at least a dozen key signaling pathways. This scenario highlights the urgent need ...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2013.02.002
更新日期:2013-04-01 00:00:00
abstract::Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumor burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs w...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.004
更新日期:2016-02-01 00:00:00
abstract::Triple negative breast cancer (TNBC) is a very aggressive subgroup of breast carcinoma, still lacking specific markers for an effective targeted therapy and with a poorer prognosis compared to other breast cancer subtypes. In this study we investigated the possibility that TNBC cells contribute to the establishment of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.015
更新日期:2014-07-01 00:00:00
abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12888
更新日期:2020-12-18 00:00:00
abstract::miRNAs in circulating extracellular vesicles (EVs) are promising biomarkers for cancer. However, their diagnostic ability for early-stage non-small-cell lung cancer (NSCLC) is not well known. In this study, the circulating EV miRNAs profiling was initially performed in 36 untreated NSCLC patients and 36 healthy contro...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12889
更新日期:2020-12-19 00:00:00
abstract::As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumu...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12756
更新日期:2020-10-01 00:00:00
abstract::A typical array experiment yields at least tens of thousands of measurements on often not more than a hundred patients, a situation often denoted as the curse of dimensionality. With a focus on prognostic multi-biomarker scores derived from microarrays, we highlight the multidimensionality of the problem and the issue...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2011.01.002
更新日期:2011-04-01 00:00:00
abstract::Although mutations in the phosphoinositide 3-kinase catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA-mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12053
更新日期:2017-05-01 00:00:00
abstract::Pancreatic cancer is one of the most lethal human cancers, and radiotherapy is often implemented for locally advanced pancreatic ductal adenocarcinoma. Tumor cell repopulation is a major challenge in treating cancers after radiotherapy. In order to address the problem of tumor repopulation, our previous studies have d...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.07.024
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients. PATIENTS AND METHODS:Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00
abstract::Deregulation of the insulin-like growth factor (IGF) axis and dysbalance of components of the IGF system as potential therapeutic targets have been described in different tumor types. IGF2 is a major embryonic growth factor and an important activator of IGF signaling. It is regulated by imprinting in a development- an...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12164
更新日期:2018-02-01 00:00:00
abstract::Targeted therapies, including antibodies, are becoming increasingly important in cancer therapy. Important limitations, however, are that not every patient benefits from a specific antibody therapy and that responses could be short-lived due to acquired resistance. In addition, targeted therapies are quite expensive a...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.03.010
更新日期:2014-06-01 00:00:00
abstract::Platinum-based chemotherapy has been the cornerstone treatment for small cell lung cancer (SCLC) for decades, but no major progress has been made in the past 20 years with regard to overcoming chemoresistance. As the cell cycle checkpoint kinase 1 (Chk1) plays a key role in DNA damage response to chemotherapeutic drug...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12882
更新日期:2020-12-15 00:00:00
abstract::Tumour suppressor p53, a master transcriptional regulator determines cell fate through preferential activation/repression of a myriad of genes during stress. Till date, activation and preferential binding of p53 on different promoters was reported to be influenced by the nature, strength and duration of stress which m...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.06.006
更新日期:2016-10-01 00:00:00
abstract::High throughput gene expression profiling has showed great promise in providing insight into molecular mechanisms. Metastasis-related mRNAs may potentially enrich genes with the ability to predict cancer recurrence, therefore we attempted to build a recurrence-associated gene signature to improve prognostic prediction...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12117
更新日期:2017-11-01 00:00:00
abstract::The GILUPI CellCollector (CC) is a novel in vivo circulating tumor cell (CTC) detection device reported to overcome the limitations of small blood sample volumes. The aim of this prospective, blinded study was to evaluate the clinical application of the CC and to compare its performance to the CellSearch (CS) system i...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12507
更新日期:2019-07-01 00:00:00
abstract::Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself. Epigenetic phenomena are mediated by se...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.04.002
更新日期:2010-06-01 00:00:00
abstract::The let-7 microRNA (miRNA) family has been implicated in the regulation of diverse cellular processes and disease pathogenesis. In cancer, loss-of-function of let-7 miRNAs has been linked to tumorigenesis via increased expression of target oncogenes. Excessive proliferation rate of tumor cells is often associated with...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.01.005
更新日期:2015-06-01 00:00:00
abstract::Protein inhibitor of activated STAT3 (PIAS3) is an endogenous suppressor of signal transducer and activator of transcription 3 (STAT3) signaling. By directly interacting with phosphorylated STAT3, PIAS3 can block the downstream transcriptional activity of STAT3, which is hyper-activated in various cancers. We previous...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12386
更新日期:2018-12-01 00:00:00
abstract::The elevated expression and activation of human telomerase reverse transcriptase (hTERT) is associated with the unlimited proliferation of cancer cells. However, the excise mechanism of hTERT regulation during carcinogenesis is not well understood. In this study, we discovered cleavage and polyadenylation specific fac...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.02.001
更新日期:2014-05-01 00:00:00