Abstract:
:We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis. Deregulated Wnt signaling is the major initiating event in most CRC cases. One mechanism whereby butyrate and other HDACis exert their anti-CRC effects is via Wnt signaling hyperactivation, which promotes CRC cell apoptosis. The histone acetylases (HATs) CBP and p300 are mediators of Wnt transcriptional activity, and play divergent roles in the downstream consequences of Wnt signaling. CBP-mediated Wnt signaling is associated with cell proliferation and stem cell maintenance; whereas, p300-mediated Wnt activity is associated with differentiation. We have found that CBP and p300 differentially affect the ability of butyrate to influence Wnt signaling, apoptosis, and proliferation. ZEB1 is a Wnt signaling-targeted gene, whose product is a transcription factor expressed at the invasive front of carcinomas where it promotes malignant progression and EMT. ZEB1 is typically a transcriptional repressor; however, when associated with p300, ZEB1 enhances transcription. These changes in ZEB1 activity likely affect the cancer cell phenotype. ZEB1 has been shown to promote resistance to chemotherapeutic agents, and expression of ZEB1 is upregulated in butyrate-resistant CRC cells that lack p300 expression. Since the expression of ZEB1 correlates with poor outcomes in cancer, ZEB represents a relevant therapeutic target. Here we propose that targeting the signaling network established by ZEB1, Wnt signaling, and p300 signaling can reverse HDACi resistance and inhibit EMT.
journal_name
J Cancerjournal_title
Journal of Cancerauthors
Lazarova D,Bordonaro Mdoi
10.7150/jca.18762subject
Has Abstractpub_date
2017-05-12 00:00:00pages
1453-1459issue
8issn
1837-9664pii
jcav08p1453journal_volume
8pub_type
杂志文章abstract::Trend analysis is the analysis using statistical models to estimate and predict potential trends over time, space or any independent continuous-variable. It has been widely used in epidemiology and public health, but much less so in clinical oncology and basic cancer research. Methodological imitations of the chosen s...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.43521
更新日期:2020-03-04 00:00:00
abstract:BACKGROUND:Mitochondria play crucial roles in cell signaling events, interorganellar communication, aging, cell proliferation and apoptosis, and mitochondrial impairment has been shown to accelerate or modulate cancer progression. Ubiquitous mitochondrial creatine kinase (uMtCK) is predominantly localized in the interm...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.13207
更新日期:2016-01-01 00:00:00
abstract::Angiogenesis, a highly regulated process, is exploited by tumors like breast cancer to ensure a constant supply of oxygen and nutrients and is key for tumor survival and progression. Estrogen and alcohol independently have been observed to contribute to angiogenesis in breast cancer but their combinatorial effects hav...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.25581
更新日期:2018-10-06 00:00:00
abstract::Objectives: LncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) is a newly discovered long non-coding RNA that aberrantly up-regulates and holds prognostic value in various tumors. The aim of the review and meta-analysis is to assess its prognostic potential and functions in maligna...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.28541
更新日期:2019-02-26 00:00:00
abstract::Early detection and accurate evaluation were both critical to improving the prognosis of clear cell Renal Cell Carcinoma (ccRCC) patients. More importantly, RNA Binding Proteins (RBPs) play a vital role in the tumorigenesis and progression of numerous cancers. However, the relationship between RBPs and ccRCC is still ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.49175
更新日期:2020-09-23 00:00:00
abstract:: Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular patho...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22318
更新日期:2018-01-01 00:00:00
abstract::Many studies, using different chemical agents, have shown excellent cancer prevention efficacy in mice and rats. However, equivalent tests of cancer prevention in humans require decades of intake of the agents while the rodents' short lifespans cannot give us information of the long-term safety. Therefore, animals wit...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.12519
更新日期:2015-09-01 00:00:00
abstract::MicroRNAs (miRNAs) have been recognized as key regulators of tumorigenesis and progression. Serum miR-302c-3p expression is prominently deregulated in HCV-related hepatocellular carcinoma (HCC). However, the expression of miR-302c-3p and its functional role in HBV-related HCC are rarely investigated. In this study, we...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.25569
更新日期:2018-06-23 00:00:00
abstract::Mechanistic target of rapamycin (mTOR) plays a critical role in the development of oral squamous cell carcinoma (OSCC), but the underlying mechanisms remain poorly understood. Here we have demonstrated that the expression of osteopontin (OPN) was dramatically up-regulated in OSCC tissues and cell lines. Moreover, redu...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.18031
更新日期:2017-05-12 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear receptor superfamily, participates in multiple physiological and pathological processes. Extensive studies have revealed the relationship between PPARγ and various tumors. However, the expression and function of PPARγ in bladder cancer s...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.42663
更新日期:2020-04-06 00:00:00
abstract::To explore the role of phospholipase D1 (PLD1) mRNA in transition of prostate cancer (PCa) cells to androgen independence, we used Arraystar Human LncRNA Microarray V3.0 to detect and compare the differential expression of PLD1 and its signaling pathway-related gene in standard androgen dependence prostate cancer (ADP...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.26689
更新日期:2018-09-08 00:00:00
abstract::Taking into account the previously reported relationship between inflammation and carcinogenesis, and the scant amount of data concerning the role of neutrophil extracellular traps (NETs) in carcinogenesis, we decided to study the process of extracellular trap formation in patients with inflammation as well as in pati...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.24238
更新日期:2018-04-30 00:00:00
abstract::Pomegranate has been shown to prolong PSA doubling time in early prostate cancer, but no data from a placebo controlled trial has been published yet. The objective of this study was to prospectively evaluate the impact of pomegranate juice in patients with prostate cancer. We conducted a phase IIb, double blinded, ran...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.7123
更新日期:2013-08-29 00:00:00
abstract::Esophageal cancer is an aggressive disease featured by early lymphatic and hematogenous dissemination, and is the sixth leading cause of cancer-related deaths worldwide. The proper formation of apicobasal polarity is essential for normal epithelium physiology and tissue homeostasis, while loss of polarity is a hallmar...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.11709
更新日期:2015-06-11 00:00:00
abstract::Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA ...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.47260
更新日期:2020-10-18 00:00:00
abstract::Purpose: This study aimed to identify the survival benefit and safety of alternative dosage schedules for sunitinib in metastatic renal cell carcinoma. Materials and Methods: Clinicopathologic and survival data of patients treated with sunitinib as first-line therapy were retrospectively reviewed. Patients were classi...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.25693
更新日期:2018-09-07 00:00:00
abstract::Cancer is a genetic disease where genetic variations cause abnormally functioning genes that appear to alter expression. Proteins, the final products of gene expression, determine the phenotypes and biological processes. Therefore, detecting gene expression levels can be used for cancer diagnosis, prognosis, and treat...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.24744
更新日期:2018-06-05 00:00:00
abstract:BACKGROUND AND AIMS:We compared clinicopathologic data and long-term clinical outcomes among patients with non-B and non-C hepatocellular carcinoma (NBNC-HCC) who underwent curative resection (group A, n=129), those with hepatitis B virus-related HCC (group B, n=62) and those with hepatitis C virus-related HCC (group C...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.6503
更新日期:2013-07-18 00:00:00
abstract::Distant metastasis is the primary cause of cancer-related death among patients with colorectal cancer (CRC), and the discovery of novel therapeutic targets by further exploring the molecular mechanisms of CRC metastasis is therefore urgently needed. We previously illustrated that CDC27 overexpression promoted prolifer...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.19381
更新日期:2017-08-21 00:00:00
abstract::Background & Aims: Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma....
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.23017
更新日期:2018-04-06 00:00:00
abstract::Background: The predictive roles of secreted protein acidic and rich in cysteine (SPARC) in pancreatic ductal adenocarcinoma (PDAC) patients after curative resection have not been clarified. We investigated the correlations between the SPARC expression and the postoperative prognosis. Methods: We retrospectively analy...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.28660
更新日期:2019-01-01 00:00:00
abstract::Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little tox...
journal_title:Journal of Cancer
pub_type: 杂志文章,评审
doi:10.7150/jca.24488
更新日期:2018-04-06 00:00:00
abstract::Purpose: To design an alternative workflow for cancer-risk assessment to predict distant metastasis (DM) of nasopharyngeal carcinoma (NPC). Methods: We enrolled 234 patients with non-disseminated NPC and a family history of cancer who underwent intensity-modulated radiotherapy and concurrent chemo-radiotherapy with/wi...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.19611
更新日期:2017-07-20 00:00:00
abstract::Purpose: We explored the influence of age on clinicopathologic features and survival of patients with M0 gastric cancer (GC). Methods: 16856 GC patients from Surveillance, Epidemiology and End Results (SEER) database and 1037 GC patients from Chinese multiple centers were enrolled in the U.S. and Chinese cohort, respe...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.22085
更新日期:2018-03-08 00:00:00
abstract::Objectives: We aimed to investigate the interaction between fasting blood glucose and tumor embolus, and the potential mediation effect of fasting blood glucose on tumor embolus in predicting gastrointestinal tract cancer-specific mortality risk postoperatively. Methods and Results: 4330 patients were consecutively re...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.34843
更新日期:2020-01-01 00:00:00
abstract::Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conduc...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.20643
更新日期:2018-02-01 00:00:00
abstract::EGFR mutation of Non-small cell lung cancers (NSCLC) was predominantly seen in Asian population and it was considered as a predictor of responsiveness. Eendothelial nitric oxide synthase (eNOS) plays a vital role in chronic inflammation and carcinogenesis. In this study, we aimed to explore the association between the...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.25824
更新日期:2018-06-15 00:00:00
abstract:BACKGROUND:Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the eff...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.11814
更新日期:2015-07-17 00:00:00
abstract::Colorectal cancer (CRC) usually gives rise to transcoelomic spread and ultimately causes peritoneal carcinomatosis (PC). However, mechanism studies, especially the immunological basis of colorectal PC, are rarely revealed due to lack of a suitable PC model. Here we selected a mouse colorectal cancer cell line MC-38 fo...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.27947
更新日期:2019-01-01 00:00:00
abstract::Background: The programmed death 1 (PD1)/programmed death ligand 1 (PDL1) targeted therapies have gained positive outcomes in several tumors, but the evidence of the expression and prognosis value of PD1/PDL1 in high risk prostate cancer was rare. Methods: Immunohistochemical analysis of PDL1/PD1 expression by a valid...
journal_title:Journal of Cancer
pub_type: 杂志文章
doi:10.7150/jca.30384
更新日期:2019-06-02 00:00:00