RRM1-induced metastasis suppression through PTEN-regulated pathways

Gautam, Anirudh; Li, Zhan Rong; Bepler, Gerold

doi:10.1038/sj.onc.1206232

Cited by 136 publications

(115 citation statements)

References 44 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…43 A recent study have shown that PTEN reduced phosphorylation of focal adhesion kinase, suppressed invasion and metastasis formation, and increased survival in an animal model. 44 Our preliminary study has indicated that PTEN could be upregulated by AST in HCT 116 cells (Supporting Information Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Auyeung

Cho

2009

Intl Journal of Cancer

View full text Add to dashboard Cite

Astragalus membranaceus has been used to ameliorate the side effects of antineoplastic drugs because of its immunomodulating nature. We had recently demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and proapoptotic properties in human colon cancer cells and tumor xenograft. In this study, we identified NSAID-activated gene (NAG-1) as a potential molecular target of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V-FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase reporter assay and electrophoretic mobility shift assay were conducted to determine the association of NAG-1 and related transcription factors with AST during its regulation of apoptotic activities. Moreover, the combined proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K-Akt pathway were also examined. AST caused overexpression of NAG-1, leading to PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug was associated with increased gene expression, in addition to prior increase in Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was intensified when PI3K inhibitor LY294002 or Akt inhibitor was cotreated and reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG-1 is a potential molecular target of AST in its antitumorigenic and proapoptotic actions, which would have additive effects when used along with PI3K-Akt inhibitors. The information obtained could facilitate future development of a novel target-specific chemotherapeutic agent with known molecular pathway. ' 2009 UICC

show abstract

Section: Discussionmentioning

confidence: 99%

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Auyeung

Cho

2009

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…By immunoblot analysis, PTEN expression was decreased in all malignant cell lines compared with normal hepatocytes ( Figure 7B). Moreover, there was an increase in constitutive tyrosine phosphorylation of FAK, an established downstream target of PTEN 17,18 FAK is a protein tyrosine kinase involved in the regulation of cell-cycle progression, cell survival, and cell migration. Expression of PTEN leads to dephosphorylation of FAK and inhibition of cell migration.…”

Section: Mir-21 Modulates Both Pten Expression and Fak Phosphorylationmentioning

confidence: 99%

MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Clinical and cell biological studies suggest that LOH is an important tumor‐suppressor gene region in lung cancer 15, 16. Moreover, RRM1 is a metastasis suppressor gene through PTEN‐regulated pathways in lung cancer 17. Furthermore, it encodes the regulatory subunit of ribonucleotide reductase which was inhibited by gemcitabine metabolites (5′ diphosphate) 18.…”

Section: Discussionmentioning

confidence: 99%

RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>Gis associated with increased susceptibility of lung cancer in Chinese patients

Zheng

Mao

et al. 2016

Cancer Medicine

View full text Add to dashboard Cite

Ribonucleotide reductase M1 (RRM1) is a crucial gene in DNA repair. Recent studies have shown that RRM1 expression can be a powerful predictor of survival or chemotherapy sensitivity in patients presenting with carcinomas who are treated with adjuvant gemcitabine‐based chemotherapy including lung cancer. However, the relationship between the single nucleotide polymorphisms (SNP) of RRM1 and the susceptibility of lung cancer to chemotherapy has not been well addressed. We detected six tag SNPs of RRM1 genotypes in a cohort of 1007 patients with primary lung cancer and 1007 age‐ and sex‐matched population controls using SNaPshot detection technology. Logistic regression, odds ratios (OR), and 95% confidence intervals were calculated to estimate lung cancer risk associated with SNP genotypes and haplotypes, after adjusting for case–control matching factors. Compared with the T/T and A/T genotype of RRM1 *151A>T, the A/A genotype had an increased risk for overall lung cancer (adjusted OR, 1.33). Additionally, the T/T+T/C genotypes of RRM1 ‐756T>C were risk factors that increased the susceptibility to lung cancer (adjusted OR 1.54, as compared with the C/C genotype). While the T/T+G/T genotypes of RRM1 ‐585T>G behaved as protective factors to increase the susceptibility to lung cancer (adjusted OR 0.44, as compared with the C/C genotype). In summary, this is the first study to systematically identify the relationship between the polymorphisms of RRM1 and individual susceptibility to lung cancer. It is anticipated that the RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>G polymorphisms will improve the predictive prognosis of lung cancer sensitivity.

show abstract

RRM1-induced metastasis suppression through PTEN-regulated pathways

Cited by 136 publications

References 44 publications

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer

RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>Gis associated with increased susceptibility of lung cancer in Chinese patients

Contact Info

Product

Resources

About