Abstract:
:Extravasation and metastatic progression are two main reasons for the high mortality rate associated with cancer. The metastatic potential of cancer cells depends on a plethora of metabolic challenges prevailing within the tumor microenvironment. To achieve higher rates of proliferation, cancer cells reprogram their metabolism, increasing glycolysis and biosynthetic activities. Just why this metabolic reprogramming predisposes cells towards increased oncogenesis remains elusive. The accumulation of myriad oncolipids in the tumor microenvironment has been shown to promote the invasiveness of cancer cells, with lysophosphatidic acid (LPA) being one such critical factor enriched in ovarian cancer patients. Cellular bioenergetic studies confirm that oxidative phosphorylation is suppressed and glycolysis is increased with long exposure to LPA in ovarian cancer cells compared with non-transformed epithelial cells. We sought to uncover the regulatory complexity underlying this oncolipid-induced metabolic perturbation. Gene regulatory networking using RNA-Seq analysis identified the oncogene ETS-1 as a critical mediator of LPA-induced metabolic alterations for the maintenance of invasive phenotype. Moreover, LPA receptor-2 specific PtdIns3K-AKT signaling induces ETS-1 and its target matrix metalloproteases. Abrogation of ETS-1 restores cellular bioenergetics towards increased oxidative phosphorylation and reduced glycolysis, and this effect was reversed by the presence of LPA. Furthermore, the bioenergetic status of LPA-treated ovarian cancer cells mimics hypoxia through induction of hypoxia-inducible factor-1α, which was found to transactivate ets-1. Studies in primary tumors generated in syngeneic mice corroborated the in vitro findings. Thus, our study highlights the phenotypic changes induced by the pro-metastatic factor ETS-1 in ovarian cancer cells. The relationship between enhanced invasiveness and metabolic plasticity further illustrates the critical role of metabolic adaptation of cancer cells as a driver of tumor progression. These findings reveal oncolipid-induced metabolic predisposition as a new mechanism of tumorigenesis and propose metabolic inhibitors as a potential approach for future management of aggressive ovarian cancer.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Ray U,Roy Chowdhury S,Vasudevan M,Bankar K,Roychoudhury S,Roy SSdoi
10.1002/1878-0261.12046subject
Has Abstractpub_date
2017-05-01 00:00:00pages
491-516issue
5eissn
1574-7891issn
1878-0261journal_volume
11pub_type
杂志文章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:PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.005
更新日期:2015-04-01 00:00:00
abstract::Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12-p11 and encodes a key DNA base excision...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.01.001
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.021
更新日期:2016-02-01 00:00:00
abstract::Estrogen receptor-alpha (ERα)-positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ERα activity requires the functional involvement of pioneer factors FOXA1 and GATA3, which enable ERα-chromatin binding and are crucial for ERα-dr...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/1878-0261.12353
更新日期:2018-11-01 00:00:00
abstract::Recently, RNAs interacting with proteins have been implicated in playing an important role in the occurrence and progression of oesophageal squamous cell carcinoma (ESCC). In this study, we found that NELFA mRNA interacts with Rad17 through a novel noncoding mode in the nucleus and that the aberrant expression of USF2...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12619
更新日期:2020-03-01 00:00:00
abstract::Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting ap...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12190
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:DNA analysis by NGS has become important to direct the clinical care of cancer patients. However, NGS is not successful in all cases, and the factors responsible for test failures have not been systematically evaluated. MATERIALS AND METHODS:A series of 1528 solid and hematolymphoid tumor specimens was tested ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.05.004
更新日期:2015-11-01 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:BACKGROUND:The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested. METHODS:We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.08.002
更新日期:2011-12-01 00:00:00
abstract::Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12193
更新日期:2018-05-01 00:00:00
abstract::There is increasing evidence that glioblastoma possess 'stem-like' cells, low concentrations of which can initiate a tumour. It has been proposed that these cells are radioresistant, and that this property contributes to the poor treatment outcomes of these tumours. In this paper we propose that radioresistance is not...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2011.05.001
更新日期:2011-08-01 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::Germ cell cancers (GCC) are the most frequent malignancy in young Caucasian males. GCC can consist of seminomas (SE) and non-seminomas (malignant NS: embryonal carcinoma (EC), yolk sac tumor (YS), choriocarcinoma (CH) and teratoma (TE)). Current serum-markers used for diagnosis and follow-up (AFP, hCG) are predominant...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.molonc.2013.08.002
更新日期:2013-12-01 00:00:00
abstract::The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by perform...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.11.002
更新日期:2011-02-01 00:00:00
abstract::Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell proliferation and oncogenesis. Here, we report that GOF p53 induces tumorigenicity through simultaneous activation of key oncogenic pathways including those controlling putative tumor-initiating cell functions. We determined that in cells expres...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12068
更新日期:2017-06-01 00:00:00
abstract::Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell-to-cell communication within the tumor microenvironment. EVs' components, such as proteins, noncoding RNAs [microRNAs (miRNAs...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12144
更新日期:2017-12-01 00:00:00
abstract::Angiogenin (ANG), a 14-kDa pro-angiogenic secreted protein, has been shown to play a role in cell migration and tumor invasion, which involve proteolytic cleavage of plasminogen to generate plasmin. However, the mechanism by which ANG regulates plasmin formation and cell migration was not known. Our studies here detec...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.12.017
更新日期:2014-05-01 00:00:00
abstract::The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.03.004
更新日期:2016-06-01 00:00:00
abstract::Prostate cancer (PCa) remains an important public health concern in Western countries. Metabolic syndrome (MeS) is a cluster of pathophysiological disorders with increasing prevalence in the general population that is a risk factor for PCa. Several studies have determined that a crosstalk between white adipose tissue ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12788
更新日期:2020-09-02 00:00:00
abstract::The absence of biomarkers to accurately predict anticancer therapy response remains a major obstacle in clinical oncology. We applied a genome-wide loss-of-function screening approach in human haploid cells to characterize genetic vulnerabilities to classical microtubule-targeting agents. Using docetaxel and vinorelbi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12307
更新日期:2018-06-01 00:00:00
abstract::Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylatio...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12785
更新日期:2020-11-01 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::The above article, published online on 28 February 2020 in Wiley Online Library (wileyonlinelibrary.com) as an Accepted Article (https://doi.org/10.1002/1878-0261.12656), has been withdrawn at the authors' request, and in agreement between the authors, the journal Editors in Chief J. E. Celis and K. Ryan, and John Wil...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12656
更新日期:2020-12-01 00:00:00
abstract::The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tiss...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12487
更新日期:2019-05-01 00:00:00
abstract::Histone methyltransferases (HMTs) catalyze the methylation of lysine and arginine residues on histone tails and non-histone targets. These important post-translational modifications are exquisitely regulated and affect chromatin compaction and transcriptional programs leading to diverse biological outcomes. There is a...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2016.09.003
更新日期:2016-12-01 00:00:00
abstract::Hydrophobic neoantigens are more immunogenic because they are better presented by the major histocompatibility complex and better recognized by T cells. Tumor cells can evade the immune response by expressing checkpoints such as programmed death ligand 1. Checkpoint blockade reactivates immune recognition and can be e...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12748
更新日期:2020-08-01 00:00:00
abstract::Cancer is a multifactorial and heterogeneous disease. The corresponding complexity appears at multiple levels: from the molecular and the cellular constitution to the macroscopic phenotype, and at the diagnostic and therapeutic management stages. The overall complexity can be approximated to a certain extent, e.g. cha...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.08.013
更新日期:2015-01-01 00:00:00
abstract::Patient derived xenografts (PDXs) are increasingly appreciated models in cancer research, particularly for preclinical testing, as they reflect the patient's tumor biology more accurately than cancer cell lines. We have established a collection of 20 breast PDXs and characterized their biological and clinical features...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章
doi:10.1016/j.molonc.2013.11.010
更新日期:2014-03-01 00:00:00
abstract::PKN3 is an AGC-family protein kinase implicated in growth of metastatic prostate cancer cells with phosphoinositide 3-kinase pathway deregulation. The molecular mechanism, however, by which PKN3 contributes to malignant growth and tumorigenesis is not well understood. Using orthotopic mouse tumor models, we now show t...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.12.001
更新日期:2012-06-01 00:00:00