Normal cellular senescence and cancer susceptibility in mice genetically deficient in Ras-induced senescence-1 (Ris1)

Nieto, Manuel; Barradas, Marta; Criado, Luis M.; Flores, Juana M.; Serrano, Manuel; Llano, Elena

doi:10.1038/sj.onc.1209978

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…Our results were consistent with the previous study that found that TMEM158 was an upregulated gene in Ras-senescent human fibroblasts and expected to negatively regulate cell cycle [ 8 ]. However, another study indicated that TMEM158-deficient mouse embryonic fibroblasts showed no apparent change in cellular functions, such as proliferation, senescence and oncogenic transformation [ 19 ]. The discrepancy may due to differences in cell types and experimental models.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TMEM158 contributes to ovarian carcinogenesis

Cheng

Guo

Chen

et al. 2015

J Exp Clin Cancer Res

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BackgroundTransmembrane protein 158 (TMEM158) is a recently identified upregulated gene during Ras-induced senescence. Its association with various cancers has been recently reported. However, the expression and biological function of TMEM158 in ovarian cancer is still unclear. This study was aimed to elucidate the roles of TMEM158 in cell proliferation, adhesion and cell invasion of ovarian cancer cells.MethodsWe analyzed TMEM158 mRNA level in ovarian cancer tissues and adjacent no-tumorous tissues by real-time PCR. We then suppressed TMEM158 expression of ovarian cancer cells by RNA interference and examined the effects of TMEM158 knockdown on cancerous transformation of ovarian cancer cells.ResultsThe RNA-sequencing data of the ovarian cancer cohort from The Cancer Genome Atlas project (TCGA) and our real-time PCR data showed that TMEM158 was overexpressed in ovarian cancer. Knockdown of TMEM158 by RNA interference in ovarian cancer cells significantly inhibited cell proliferation, which may be due to the increase of G1-phase arrest. Silencing of TMEM158 also inhibited cell adhesion, cell invasion as well as tumorigenicity in nude mice. Moreover, knockdown of TMEM158 notably repressed cell adhesion via down-regulating the expression intercellular adhesion molecule1 (ICAM1) and vascular cell adhesion molecule1 (VCAM1). Transforming Growth Factor-β (TGF-β) signaling pathway was also remarkably impaired by TMEM158 silencing.ConclusionsOur data suggests that TMEM158 may work as an oncogene for ovarian cancer and that inhibition of TMEM158 may be a therapeutic strategy for ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Overexpression of TMEM158 contributes to ovarian carcinogenesis

Cheng

Guo

Chen

et al. 2015

J Exp Clin Cancer Res

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“…Other studies have implicated a role for Rasl11b subgroup members in oncogenesis. For instance, rasl11a mRNA is less abundant in some prostate cancers [38] , ris / rasl12 tumor suppressor function in breast cancer is controversial [37] , [62] , and rerg expression inhibits tumor formation in nude mice and is decreased or lost in primary human breast tumors [39] . Thus, clarifying the biological role of this subgroup of small GTPase necessitates further studies.…”

Section: Discussionmentioning

confidence: 99%

Rasl11b Knock Down in Zebrafish Suppresses One-Eyed-Pinhead Mutant Phenotype

et al. 2008

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The EGF-CFC factor Oep/Cripto1/Frl1 has been implicated in embryogenesis and several human cancers. During vertebrate development, Oep/Cripto1/Frl1 has been shown to act as an essential coreceptor in the TGFβ/Nodal pathway, which is crucial for germ layer formation. Although studies in cell cultures suggest that Oep/Cripto1/Frl1 is also implicated in other pathways, in vivo it is solely regarded as a Nodal coreceptor. We have found that Rasl11b, a small GTPase belonging to a Ras subfamily of putative tumor suppressor genes, modulates Oep function in zebrafish independently of the Nodal pathway. rasl11b down regulation partially rescues endodermal and prechordal plate defects of zygotic oep−/− mutants (Zoep). Rasl11b inhibitory action was only observed in oep-deficient backgrounds, suggesting that normal oep expression prevents Rasl11b function. Surprisingly, rasl11b down regulation does not rescue mesendodermal defects in other Nodal pathway mutants, nor does it influence the phosphorylation state of the downstream effector Smad2. Thus, Rasl11b modifies the effect of Oep on mesendoderm development independently of the main known Oep output: the Nodal signaling pathway. This data suggests a new branch of Oep signaling that has implications for germ layer development, as well as for studies of Oep/Frl1/Cripto1 dysfunction, such as that found in tumors.

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“…RIS1 has recently been identified as a target in the mutator pathway of colorectal cancers exhibiting microsatellite instability, where mutations have been observed in the CGN codon repeat tract that encodes 14 alanines 68. In order to deduce the molecular function of the gene, a homozygous RIS1 ‐null mouse knockout was created recently 69. Although there were no overt changes in embryonic development, adult physiology, or frequency of tumor formation, following chemical induction, further studies are warranted as a modest (although not statistically significant) increase in tumor size was observed in the RIS1 ‐null mice.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of serous ovarian cancers identifies differentially expressed chromosome 3 genes

Birch

Quinn

Filali‐Mouhim

et al. 2007

Molecular Carcinogenesis

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Cytogenetic, molecular genetic and functional analyses have implicated chromosome 3 genes in epithelial ovarian cancers (EOC). To further characterize their contribution to EOC, the Affymetrix U133A GeneChip 1 was used to perform transcriptome analyses of chromosome 3 genes in primary cultures of normal ovarian surface epithelial (NOSE) cells (n ¼ 14), malignant serous epithelial ovarian tumors (TOV) (n ¼ 17), and four EOC cell lines (TOV-81D, TOV-112D, TOV-21G, and OV-90). A two-way comparative analysis of 735 known genes and expressed sequences identified 278 differentially expressed genes, where 43 genes were differentially expressed in at least 50% of the TOV samples. Three genes, RIS1 (at 3p21.31), GBE1 (at 3p12.2), and HEG1 (at 3q21.2), were similarly underexpressed in all TOV samples. Deregulation of the expression of these genes was not associated with loss of heterozygosity (LOH) of the genetic loci harboring them. LOH analysis of the RIS1, GBE1, and HEG1 loci was observed at frequencies of 14.3%, 13.7%, and 9.2%, respectively, in a series of 66 malignant TOV samples of the serous subtype. Reduced expression levels of RIS1, GBE1, and HEG1 were observed only in the tumorigenic EOC cell lines (TOV-21G, TOV-112D, and OV-90) and did not correlate with LOH. These results combined suggest that RIS1, GBE1, and HEG1, unlike classical tumor suppressor genes, are not likely to be primary targets of inactivation. This study provides a comprehensive analysis of chromosome 3 gene expression in NOSE and in EOC samples and identifies chromosome 3 gene candidates for further study. ß 2007 Wiley-Liss, Inc.

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Normal cellular senescence and cancer susceptibility in mice genetically deficient in Ras-induced senescence-1 (Ris1)

Cited by 4 publications

References 20 publications

Overexpression of TMEM158 contributes to ovarian carcinogenesis

Overexpression of TMEM158 contributes to ovarian carcinogenesis

Rasl11b Knock Down in Zebrafish Suppresses One-Eyed-Pinhead Mutant Phenotype

Transcriptome analysis of serous ovarian cancers identifies differentially expressed chromosome 3 genes

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