Abstract:
:Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. As tumor metastasis is the leading cause of death in patients with CRC, it is important to elucidate the molecular mechanisms that drive CRC metastasis. Studies have shown a close relationship between Iroquois homeobox (IRX) family genes and multiple cancers, while the mechanism by which IRX5 promotes CRC metastasis is unclear. Therefore, we focused on the involvement of IRX5 in CRC metastasis. In this study, analyses of clinical data indicated that the expression of IRX5 was coincided with metastatic colorectal tumors tissues and was negatively correlated with the overall survival of patients with CRC. Functional analysis showed that IRX5 promoted the migration and invasion of CRC cells, accompanied by a large number of cellular protrusions. IRX5-overexpressing cells were more likely to form metastatic tumors in nude mice. Further analysis demonstrated that the core components of the RHOA/ROCK1/LIMK1 pathway were significantly inhibited in IRX5-overexpressing cells. Overexpression of LIMK1 effectively reversed the enhanced cellular motility caused by IRX5 overexpression. Moreover, we found that high levels of IRX5 in intestinal tissues were correlated with the inflammatory response. IRX5 was significantly increased in azoxymethane/dextran sodium sulfate intestinal tissue of mice and IRX5-overexpressing may also enhance chemokines CXCL1 and CXCL8. In summary, our findings suggested that IRX5 promoted CRC metastasis by inhibiting the RHOA-ROCK1-LIMK1 axis, which correlates with a poor prognosis.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Zhu Q,Wu Y,Yang M,Wang Z,Zhang H,Jiang X,Chen M,Jin T,Wang Tdoi
10.1002/mc.23098subject
Has Abstractpub_date
2019-11-01 00:00:00pages
2065-2076issue
11eissn
0899-1987issn
1098-2744journal_volume
58pub_type
杂志文章abstract::Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic paramet...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20653
更新日期:2010-09-01 00:00:00
abstract::Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNC...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22825
更新日期:2018-08-01 00:00:00
abstract::The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940120102
更新日期:1995-01-01 00:00:00
abstract::The ubiquitin-proteasome pathway is fundamental to synchronized continuation of many cellular processes, for example, cell-cycle progression, stress response, and cell differentiation. Recent studies have shown that the ubiquitin-proteasome pathway functions in the regulation of nucleotide excision repair (NER) in yea...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20065
更新日期:2005-01-01 00:00:00
abstract::Ultraviolet (UV) light-induced activation of activator protein-1 (AP-1), resulting at least in part from oxidative stress, promotes skin carcinogenesis. It has not yet been determined whether elevating cellular phase II enzymes and glutathione (GSH) levels inhibits the AP-1 activation. We have, therefore, examined the...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20052
更新日期:2004-11-01 00:00:00
abstract::Composition of extracellular matrix (ECM) is crucial to the establishment and maintenance of epithelial apical-basolateral polarity. Increased ECM rigidity caused by deposition of fibrillar collagen, for example, collagen type I (Col-1), promotes loss of epithelial polarity and tumor progression. microRNAs are small n...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20742
更新日期:2011-07-01 00:00:00
abstract::To analyze the mechanism of neoplastic transformation of rodent diploid cells by ras and myc oncogenes, human EJ c-Ha-ras and mouse c-myc second and third exons promoted by SV40 promoter were connected to pSV2neo and pSV2gpt, respectively. Mouse and rat primary fetal cells cotransfected with both genes formed transfor...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010404
更新日期:1989-01-01 00:00:00
abstract::Development of chemoresistance in androgen-refractory prostate cancer cells is partly due to constitutive activation of Rel/NF-kappaB transcription factors that regulate several cell survival and anti-apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of wh...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20447
更新日期:2008-12-01 00:00:00
abstract::RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20598
更新日期:2010-03-01 00:00:00
abstract::The identification of cancer-associated long non-coding RNAs (lncRNAs) and the investigation of their molecular and biological functions are vital for understanding the molecular biology and progression of cancer. The lncRNA-LET, a newly identified lncRNA, was demonstrated to be down-regulated in hepatocellular cancer...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22215
更新日期:2015-11-01 00:00:00
abstract::Here, we have demonstrated that xenobiotic activation of the nuclear receptor (CAR, NR1I3) can result in arresting DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase. Huh7 cells over-expressing CAR were either treated with dimethyl sulfoxide, the CAR activator TCPOBOP (1,4-bis[2-(3,5-dichloropyrid...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20783
更新日期:2012-02-01 00:00:00
abstract::The relationship between thyroid hormone (triiodothyronine, T(3)) and breast cancer is unclear. We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor (TR alpha 1), of its ligand T(3), and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacit...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10046
更新日期:2002-05-01 00:00:00
abstract::Emerging evidence has shown the association of aberrantly expressed miR-106a with cancer development, however, little is known about its potential role in gastric carcinogenesis. In our present study, obviously overexpressed miR-106a was found in gastric cancer tissues compared with their nontumor counterparts. Suppre...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21899
更新日期:2013-08-01 00:00:00
abstract::N-acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4-aminobiphenyl (ABP). NAT1 catalyzes N-acetylation of arylamines as well as the O-acetylation of N-hydroxylated arylamines. O-acetylation leads to the formation of e...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20836
更新日期:2012-08-01 00:00:00
abstract::Cytokines are considered to play an important role in tumor pathogenesis and progression, and recent studies have demonstrated that a variety of forms, including interleukins (ILs) and transforming growth factor-beta(s) (TGF-beta(s)), may regulate tumors. In the present study, the expression of TGF-beta isoforms and I...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) are carcinogens found in cooked meats that form DNA adducts upon metabolic activation. Purified DNA from Chinese hamster ovary (CHO) cells was reacted in vitro with the active metabolites N-acetoxy-IQ or N-acetoxy-Me...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940070211
更新日期:1993-01-01 00:00:00
abstract::The vaccinia virus cDNA expression system was used to produce human cytochrome P450 IA2 in a hepatoma cell line that is devoid of significant basal levels of P450. The expressed enzyme yielded a reduced carbon monoxide-bound difference spectrum with a lambda max of 449 nm. Catalytic activities and mutagen activation a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940020405
更新日期:1989-01-01 00:00:00
abstract::Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. There is clear evidence that cytochrome P450 (CYP) 3A enzymes play an important role in TAM metabolism, resulting in metabolites that lead to formation of TAM-DNA adducts. We have investigated the effect of CYP3A2 antisense (AVI-4472) exp...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20143
更新日期:2006-02-01 00:00:00
abstract::The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cl...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940060204
更新日期:1992-01-01 00:00:00
abstract::DNA hypermethylation is associated with decreased expression of tumor suppressor genes. We previously observed decreased Fhit expression and Fhit promoter region hypermethylation in rodent tumors induced by various carcinogens, and noted that the 5' regulatory regions in the promoter, exon 1, and intron 1 were differe...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20100
更新日期:2005-07-01 00:00:00
abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant mutagenic heterocyclic amine in cooked foods. Two mouse tumor cell lines, BMT11 and FM3A, were exposed to its proximate form, 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP). Fifty-six subclones of BMT11 and 39 subclones of ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090203
更新日期:1994-02-01 00:00:00
abstract::Cytogenetic and molecular studies of human renal cell carcinoma (RCC) have suggested that the genetic and functional losses of one or more putative tumor suppressor genes on the short arm of chromosome 3 play a crucial role in the development of this disease. To examine whether the introduction of chromosome 3 has any...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090303
更新日期:1994-03-01 00:00:00
abstract::Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22506
更新日期:2017-02-01 00:00:00
abstract::There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these mole...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22503
更新日期:2017-02-01 00:00:00
abstract::The MN/CA9 (G250) gene expressed in the normal alimentary tract in a tissue-specific manner is often activated in renal cell carcinomas. To cast light on the activation mechanism, we examined the methylation status of this gene in seven human renal cell carcinoma cell lines (SKRC-01, -06, -10, -12, -14, -44, and -59) ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::The effects of rat-specific hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), mouse-specific hepatocarcinogen ortho-aminoazotoluene (OAT), non-species-specific hepatocarcinogen diethylnitrosamine (DENA), and non-carcinogenic 4'-methyl-4-dimethylaminoazobenzene (4'-MeDAB) on glucocorticoid induction of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20090
更新日期:2005-12-01 00:00:00
abstract::Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21976
更新日期:2014-02-01 00:00:00
abstract::Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 g...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22476
更新日期:2017-01-01 00:00:00
abstract::Palliative treatment options for human cholangiocarcinoma (CCC) are quite limited and new therapeutic strategies are of utmost need. c-MET has been shown to be deregulated in many cancers, but the role of c-MET in the carcinogenesis of CCC remains unclear. The main purpose of this study is to evaluate the expression a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22449
更新日期:2016-12-01 00:00:00
abstract::To assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non-small-cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20819
更新日期:2012-07-01 00:00:00