RanGTPase: A Candidate for Myc-Mediated Cancer Progression

Yuen, Hiu‐Fung; Gunasekharan, Vignesh; Chan, Ka‐Kui; Zhang, Shudong; Platt-Higgins, Angela; Gately, Kathy; O’Byrne, K.J.; Fennell, Dean A.; Johnston, Patrick G.; Rudland, Philip S.; El‐Tanani, Mohamed

doi:10.1093/jnci/djt028

Cited by 37 publications

(65 citation statements)

References 36 publications

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“…Microarray gene expression data were retrieved from the data matrixes deposited to the GEO database by the original authors. R scripting was used to extract the expression values from probesets of VEGFA, FLT1 and KDR, and the clinical data was obtained from the data matrixes downloaded from the GEO database, as previously described (18).…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer

Zhang¹,

McCrudden

Kwok³

2015

Oncology Letters

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Abstract. Angiogenesis is important in cancer progression. Promising results in clinical trials have indicated that targeting vascular epidermal growth factor (VEGF) signaling may prolong lung cancer patient survival. In particular, various studies have implicated VEGFA as a potential prognostic marker in lung cancer, although prognostication using the expression of VEGF receptors (VEGFRs), such as fms-related tyrosine kinase 1 (FLT1; also known as VEGFR1) and kinase insert domain receptor (KDR; also known as VEGFR2), has produced varied results in different lung cancer studies. The present study aimed to investigate the prognostic significance of these three factors, alone or in combination. mRNA expression data were extracted from four independent lung cancer cohorts totaling 583 patients, and the association between mRNA expression and survival was investigated by performing statistical analyses. When VEGFA, FLT1 and KDR expression were considered alone, only VEGFA demonstrated a significant association with patient survival consistently across all four datasets (P<0.05). Patients with a high expression of VEGFA and one of the two receptors were associated with significantly worse survival than patients expressing low levels of VEGFA and the particular receptor (P<0.05). Notably, patients with a high level expression of all three genes in their tumor specimens were associated with a significantly shorter survival time compared with patients exhibiting a low level expression of one, two or all three genes (P<0.05). The results indicate that a high level of VEGFA expression and its receptors may be required for cancer progression. Therefore, these three factors should be considered together as a prognostic indicator for lung cancer patients.

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Section: Methodsmentioning

confidence: 99%

Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer

Zhang¹,

McCrudden

Kwok³

2015

Oncology Letters

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“…We analyzed 3 public gene expression profile (GEP) microarray datasets: the GSE12276 dataset consisting of 204 primary breast cancer specimens from patients with metastatic disease (31); the GSE5851 dataset consisting of 80 colorectal cancer specimens taken from patients prior to treatment with cetuximab (39); and the GSE4342 dataset consisting of a panel of NSCLC cell lines analyzed for sensitivity to and resistance against gefitinib treatment (41). All datasets were retrieved from the Gene Expression Omnibus (GEO) database and processed using R scripting as previously described (65). Since all 3 datasets were assayed on Affymetrix HG-U133 platforms, we used the average expression level for PRL-3/PTP4A3 probe sets ("206574_s_at" and "209695_at") or PTP1B/ PTPN1 probe sets ("202716_at", "217686_at", "217689_at" and "239526_x_ at") for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells

et al. 2013

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Metastasis-associated phosphatase of regenerating liver-3 (PRL-3) has pleiotropic effects in driving cancer progression, yet the signaling mechanisms of PRL-3 are still not fully understood. Here, we provide evidence for PRL-3-induced hyperactivation of EGFR and its downstream signaling cascades in multiple human cancer cell lines. Mechanistically, PRL-3-induced activation of EGFR was attributed primarily to transcriptional downregulation of protein tyrosine phosphatase 1B (PTP1B), an inhibitory phosphatase for EGFR. Functionally, PRL-3-induced hyperactivation of EGFR correlated with increased cell growth, promigratory characteristics, and tumorigenicity. Moreover, PRL-3 induced cellular addiction to EGFR signaling, as evidenced by the pronounced reversion of these oncogenic attributes upon EGFR-specific inhibition. Of clinical significance, we verified elevated PRL-3 expression as a predictive marker for favorable therapeutic response in a heterogeneous colorectal cancer (CRC) patient cohort treated with the clinically approved anti-EGFR antibody cetuximab. The identification of PRL-3-driven EGFR hyperactivation and consequential addiction to EGFR signaling opens new avenues for inhibiting PRL-3-driven cancer progression. We propose that elevated PRL-3 expression is an important clinical predictive biomarker for favorable anti-EGFR cancer therapy.

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“…Measurement of Ran activity was captured using a Ran activation assay kit (Yuen et al, 2013) (Cell Biolabs, San Diego, CA) and used according to the manufacturer instructions. This Ran activation assay is used to visualise a Ran-GTP band, which means Ran is in its active form.…”

Section: Ran Activation Assaymentioning

confidence: 99%

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells

Haggag

Matchett

Dakir

et al. 2017

International Journal of Pharmaceutics

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RanGTPase: A Candidate for Myc-Mediated Cancer Progression

Abstract: Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.

Cited by 37 publications

References 36 publications

Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer

Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer

Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells

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