IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway.

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 Carcinog

journal_title

Molecular carcinogenesis

authors

Zhu Q,Wu Y,Yang M,Wang Z,Zhang H,Jiang X,Chen M,Jin T,Wang T

doi

10.1002/mc.23098

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

2065-2076

issue

11

eissn

0899-1987

issn

1098-2744

journal_volume

58

pub_type

杂志文章
  • Prognostic implications of ezrin expression in human hepatocellular carcinoma.

    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

    authors: Kang YK,Hong SW,Lee H,Kim WH

    更新日期:2010-09-01 00:00:00

  • Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53-mediated apoptosis in LNCaP prostate cancer cells.

    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

    authors: Wu W,Karelia D,Pramanik K,Amin SG,Sharma AK,Jiang C,Lu J

    更新日期:2018-08-01 00:00:00

  • A p53 mutation in exon 5 associated with adenovirus transformation.

    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

    authors: Eyler YL,Siwarski DF,Huppi KE,Lewis AM Jr

    更新日期:1995-01-01 00:00:00

  • Cellular ubiquitination and proteasomal functions positively modulate mammalian nucleotide excision repair.

    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

    authors: Wang QE,Wani MA,Chen J,Zhu Q,Wani G,El-Mahdy MA,Wani AA

    更新日期:2005-01-01 00:00:00

  • Phase II enzyme inducer, sulforaphane, inhibits UVB-induced AP-1 activation in human keratinocytes by a novel mechanism.

    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

    authors: Zhu M,Zhang Y,Cooper S,Sikorski E,Rohwer J,Bowden GT

    更新日期:2004-11-01 00:00:00

  • Post-transcriptional up-regulation of miR-21 by type I collagen.

    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

    authors: Li C,Nguyen HT,Zhuang Y,Lin Y,Flemington EK,Guo W,Guenther J,Burow ME,Morris GF,Sullivan D,Shan B

    更新日期:2011-07-01 00:00:00

  • Cotransfection of plasmids with ras and myc oncogenes to diploid cells derived from rodent fetuses: alteration of neoplastic transformation frequency depending on the gestation period.

    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

    authors: Yagi T,Sasayama S,Sasai H,Kakunaga T

    更新日期:1989-01-01 00:00:00

  • Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells.

    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

    authors: Rabi T,Shukla S,Gupta S

    更新日期:2008-12-01 00:00:00

  • A novel tumor suppressor gene RhoBTB2 (DBC2): frequent loss of expression in sporadic breast cancer.

    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

    authors: Mao H,Qu X,Yang Y,Zuo W,Bi Y,Zhou C,Yin H,Deng B,Sun J,Zhang L

    更新日期:2010-03-01 00:00:00

  • Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer.

    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

    authors: Ma MZ,Kong X,Weng MZ,Zhang MD,Qin YY,Gong W,Zhang WJ,Quan ZW

    更新日期:2015-11-01 00:00:00

  • The nuclear receptor constitutive active/androstane receptor arrests DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase.

    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

    authors: Kamino H,Negishi M

    更新日期:2012-02-01 00:00:00

  • Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells.

    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

    authors: González-Sancho JM,Figueroa A,López-Barahona M,López E,Beug H,Muñoz A

    更新日期:2002-05-01 00:00:00

  • miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS.

    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

    authors: Wang Z,Liu M,Zhu H,Zhang W,He S,Hu C,Quan L,Bai J,Xu N

    更新日期:2013-08-01 00:00:00

  • NATb/NAT1*4 promotes greater arylamine N-acetyltransferase 1 mediated DNA adducts and mutations than NATa/NAT1*4 following exposure to 4-aminobiphenyl.

    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

    authors: Millner LM,Doll MA,Cai J,States JC,Hein DW

    更新日期:2012-08-01 00:00:00

  • Differential expression of cytokines in rat osteosarcoma and malignant fibrous histiocytoma cell lines induced by 4-(hydroxyamino)quinoline-1-oxide.

    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:

    authors: Honoki K,Tsujiuchi T,Sasaki Y,Tsutsumi M,Morishita T,Kido A,Miyauchi Y,Mii Y,Takakura Y,Konishi Y

    更新日期:2002-02-01 00:00:00

  • Quantitation of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline DNA adducts in specific sequences using alkali or uvrABC excinuclease.

    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

    authors: Nouso K,Bohr VA,Schut HA,Snyderwine EG

    更新日期:1993-01-01 00:00:00

  • Human cDNA-expressed cytochrome P450 IA2: mutagen activation and substrate specificity.

    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

    authors: Aoyama T,Gonzalez FJ,Gelboin HV

    更新日期:1989-01-01 00:00:00

  • Reduction in tamoxifen-induced CYP3A2 expression and DNA adducts using antisense technology.

    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

    authors: Mahadevan B,Arora V,Schild LJ,Keshava C,Cate ML,Iversen PL,Poirier MC,Weston A,Pereira C,Baird WM

    更新日期:2006-02-01 00:00:00

  • Molecular cloning, analysis, and chromosomal localization of a mouse genomic sequence related to the human papillomavirus type 18 E5 region.

    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

    authors: Kahn T,Friesl H,Copeland NG,Gilbert DJ,Jenkins NA,Gissmann L,Kramer J,zur Hausen H

    更新日期:1992-01-01 00:00:00

  • Hypermethylation patterns in the Fhit regulatory region are tissue specific.

    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

    authors: Guler G,Iliopoulos D,Han SY,Fong LY,Lubet RA,Grubbs CJ,Huebner K

    更新日期:2005-07-01 00:00:00

  • 2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine induction of recombinational mutations in mammalian cell lines as detected by DNA fingerprinting.

    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

    authors: Kitazawa T,Kominami R,Tanaka R,Wakabayashi K,Nagao M

    更新日期:1994-02-01 00:00:00

  • In vitro growth suppression and morphological change in a human renal cell carcinoma cell line by the introduction of normal chromosome 3 via microcell fusion.

    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

    authors: Yoshida MA,Shimizu M,Ikeuchi T,Tonomura A,Yokota J,Oshimura M

    更新日期:1994-03-01 00:00:00

  • Cinnamon extract reduces VEGF expression via suppressing HIF-1α gene expression and inhibits tumor growth in mice.

    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

    authors: Zhang K,Han ES,Dellinger TH,Lu J,Nam S,Anderson RA,Yim JH,Wen W

    更新日期:2017-02-01 00:00:00

  • Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.

    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

    authors: Gong J,Muñoz AR,Pingali S,Payton-Stewart F,Chan DE,Freeman JW,Ghosh R,Kumar AP

    更新日期:2017-02-01 00:00:00

  • Activation of the MN/CA9 gene is associated with hypomethylation in human renal cell carcinoma cell lines.

    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:

    authors: Cho M,Grabmaier K,Kitahori Y,Hiasa Y,Nakagawa Y,Uemura H,Hirao Y,Ohnishi T,Yoshikawa K,Ooesterwijk E

    更新日期:2000-03-01 00:00:00

  • Species-specific effects of the hepatocarcinogens 3'-methyl-4-dimethyl-aminoazobenzene and ortho-aminoazotoluene in mouse and rat liver.

    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

    authors: Merkulova TI,Kropachev KY,Timofeeva OA,Vasiliev GV,Levashova ZB,Ilnitskaya SI,Kobzev VF,Pakharukova MY,Bryzgalov LO,Kaledin VI

    更新日期:2005-12-01 00:00:00

  • Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India.

    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

    authors: Raman R,Kotapalli V,Adduri R,Gowrishankar S,Bashyam L,Chaudhary A,Vamsy M,Patnaik S,Srinivasulu M,Sastry R,Rao S,Vasala A,Kalidindi N,Pollack J,Murthy S,Bashyam M

    更新日期:2014-02-01 00:00:00

  • Significance of FGF9 gene in resistance to anti-EGFR therapies targeting colorectal cancer: A subset of colorectal cancer patients with FGF9 upregulation may be resistant to anti-EGFR therapies.

    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

    authors: Mizukami T,Togashi Y,Naruki S,Banno E,Terashima M,de Velasco MA,Sakai K,Yoneshige A,Hayashi H,Fujita Y,Tomida S,Nakajima TE,Fujino T,Boku N,Ito A,Nakagawa K,Nishio K

    更新日期:2017-01-01 00:00:00

  • Targeting c-MET by LY2801653 for treatment of cholangiocarcinoma.

    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

    authors: Barat S,Bozko P,Chen X,Scholta T,Hanert F,Götze J,Malek NP,Wilkens L,Plentz RR

    更新日期:2016-12-01 00:00:00

  • Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis.

    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

    authors: Dong J,Hu Z,Shu Y,Pan S,Chen W,Wang Y,Hu L,Jiang Y,Dai J,Ma H,Jin G,Shen H

    更新日期:2012-07-01 00:00:00