Activated Src abrogates the Myc requirement for the G
 0
 /G
 1
 transition but not for the G
 1
 /S transition

Prathapam, Tulsiram; Tegen, Sarah B.; Oskarsson, Thordur; Trumpp, Andreas; Martin, G S

doi:10.1073/pnas.0511186103

Cited by 43 publications

(37 citation statements)

References 35 publications

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“…c-Myc is associated with a wide range of cancers and is an essential regulator of G1/S transition (49,50). While in normal cells inhibition of c-Myc usually results in a G0/G1 cell cycle arrest (51,52), tumour cells exhibit significant heterogeneity with regard to the positioning of cell cycle arrest in response to c-Myc depletion (53). Cannell et al (54) showed that in response to DNA damage c-Myc is translationally repressed by the induction of miR-34c microRNA and that this induction is induced by p38 MAPK/MK2 signalling resulting in S-phase arrest.…”

Section: Discussionmentioning

confidence: 99%

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

et al. 2012

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Abstract. Different studies describe the anti-inflammatory effects of Scrophularia species, a medicinal plant widely used in folk medicine since ancient times. As knowledge regarding the anti-neoplastic properties of this species is rather limited, we investigated the influence of methanol extracts of different Scrophularia species on cell proliferation, cell death, and tumour cell intravasation through the lymph endothelial barrier. HL-60 leukaemia cells were treated with methanol extracts of different Scrophularia species leading to strong growth inhibition and high cell death rates. The expression of cell cycle regulators, oncogenes and cell death inducers was determined by Western blot analysis. Furthermore the effect of S. lucida was studied in an NF-κB reporter assay, and in a novel assay measuring 'circular chemo-repellent-induced defects' (CCID) in lymph endothelial monolayers that were induced by MCF-7 breast cancer spheroids. Methanol extracts of Scrophularia species exhibited strong anti-proliferative properties. S. floribunda extract inhibited G2/M-and later on S-phase and S. lucida inhibited S-phase and in both cases this was associated with the down-regulation of c-Myc expression. Extracts of S. floribunda and S. lucida led to necrosis and apoptosis, respectively. Furthermore, S. lucida, but not S. floribunda, effectively attenuated tumour cell intravasation through lymph endothelial cell monolayers, which correlated with the inhibition of NF-κB. S. lucida exhibited promising anti-neoplastic effects and this was most likely due to the downregulation of various cell cycle regulators, proto-oncogenes and NF-κB and the activation of caspase-3.

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Section: Discussionmentioning

confidence: 99%

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

et al. 2012

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“…It has been reported that c-SRC is involved in multiple signaling pathways, including RAS/RAF/ERK1/2, PI3K/AKT/ HIF-1a, STAT3/c-MYC/CYCLIND1, B-CATENIN/c-MYC/CYCLIND1, FAK/p130CAS/MMP9 and RAC/NADPH, which induce the growth, survival and migration of various types of cancer cells. [39][40][41] The ability to target c-SRC transcripts signifies that miR-205 might be a potential regulator of the FAK/ERK1/2 pathways in PCa cells. Western blot analysis showed that the expression levels of the members of the FAK/ ERK1/2 pathway were reduced through targeting with c-SRC after miR-205 overexpression (Figure 4b).…”

Section: Mir-205 Suppresses Tumor Growth In Vivomentioning

confidence: 99%

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

Wang¹,

Li²,

Feng³

et al. 2013

Asian J Androl

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The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen (PSA) level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRC was identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.

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“…Cell line-specific effects of c-Myc depletion A large body of literature suggests that inhibition of c-Myc in primary cells or non-transformed cell lines generally leads to a strong proliferative arrest in the G 0 / G 1 or G 1 /S phases of the cell cycle (Prochownik et al, 1988;Mateyak et al, 1997;de Alboran et al, 2001;Prathapam et al, 2006). In order to determine whether this is also the case for tumor cells, we used propidium iodide (PI) staining and flow cytometry to evaluate the cell cycle parameters of the above-described cells 4-5 days after infection ( Figure S3B), we conclude that c-Myc depletion blocks cell cycle progression in these cells equally in all phases.…”

Section: Myc-dependent Cell Cycle Regulation In Tumor Cells H Wang Et Almentioning

confidence: 99%

“…In normal cells, inhibition of c-Myc invariably results in a G 0 /G 1 cell cycle arrest (Prochownik et al, 1988;Mateyak et al, 1997;de Alboran et al, 2001;Prathapam et al, 2006). The type of cell cycle arrest caused by c-Myc depletion in tumor cells has not been adequately studied.…”

Section: Introductionmentioning

confidence: 99%

c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle

et al. 2007

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Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition

Cited by 43 publications

References 35 publications

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle

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Activated Src abrogates the Myc requirement for the G 0 /G 1 transition but not for the G 1 /S transition

Cited by 43 publications

References 35 publications

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle

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Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition