Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity

Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Benedek, Anett; Lumniczky, Katalin; Sáfrány, Géza; Hegyesi, Hargita

doi:10.1016/j.mrgentox.2015.06.009

Cited by 30 publications

(26 citation statements)

References 39 publications

(36 reference statements)

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“…To our knowledge, this is one of the first in vivo studies comparing the differences in gene and pathway expression in RT naïve HNC vs recurrent previously irradiated HNC samples. Our study identified a differential expression of various genes, with previously described associations with HNC stem cells, proliferation, and radioresistance . Most notably, our post‐RT samples had a significant downregulation of the Wnt and Myc pathways.…”

Section: Discussionsupporting

confidence: 75%

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Alterations in genetic pathways following radiotherapy for head and neck cancer

et al. 2019

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Background: Radiotherapy (RT) is an integral component in the treatment of head and neck cancer (HNC).We hypothesized there would be alterations in gene-expression and pathway activity in HNC samples obtained in recurrent HNC that were previously treated with RT, when compared to RT-naïve disease. Methods: Patient data was abstracted from a prospectively maintained database. Linear-microarray analysis and supervised gene-set enrichment-analysis were employed to compare RT-naive and recurrent disease after prior-RT. Results: A total of 157 patients were analyzed, 96 (61%) were RT-naive and 61 (39%) had RT.After radiation, there was upregulation of genes associated with angiogenesis, protein-translation-machinery, cell-cycle regulation, and growth factors, and downregulation associated with Myc activity, and hypoxic response (all P < .001).Previously irradiated HNC was associated with downregulation in 19/42 genes in the Wnt/B-catenin-pathway (P = .045)and 119/199 genes involved in the MYC target pathway (P = .024). Conclusion: Patients with recurrences salvaged surgically post-RT had significant alterations in gene-expression and in Wnt/B-catenin and MYC-target pathways. These pathways may represent potential targets to prevent development of resistance to RT.

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Section: Discussionsupporting

confidence: 75%

“…Post‐RT samples had a significant change in the expression of 251 genes, some of which have been associated with tumor suppression, radiosensitivity, hypoxic induction, and angiogenesis …”

Section: Discussionmentioning

confidence: 99%

Alterations in genetic pathways following radiotherapy for head and neck cancer

et al. 2019

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“…6A and B). GDF-15 is an important growth factor for prostate tumor progression and resistance to cytotoxic agents and radiotherapy in prostate cancer and other cancers (36)(37)(38)(39)(40)(41). Upon GDF-15 silencing (Fig.…”

Section: Identification Of Gdf-15 As a Specific Pace4 Substrate And Pmentioning

confidence: 99%

PACE4 Undergoes an Oncogenic Alternative Splicing Switch in Cancer

et al. 2017

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Inhibition of PACE4, a proprotein convertase that is overexpressed in prostate cancer, has been shown to block cancer progression in an androgen-independent manner. However, the basis for its overexpression and its growth-inhibitory effects are mitigated and uncertain. Here, we report that PACE4 pre-mRNA undergoes DNA methylation-sensitive alternative splicing of its terminal exon 3 0 untranslated region, generating an oncogenic, C-terminally modified isoform (PACE4-altCT). We found this isoform to be strongly expressed in prostate cancer cells, where it displayed an enhanced autoactivating process and a distinct intracellular routing that prevented its extracellular secretion. Together, these events led to a dramatic increase in processing of the progrowth differentiation factor pro-GDF15 as the first PACE4 substrate to be identified in prostate cancer. We detected robust expression of PACE4-altCT in other cancer types, suggesting that an oncogenic switch for this proenzyme may offer a therapeutic target not only in advanced prostate cancer but perhaps also more broadly in human cancer. Cancer Res; 77(24); 6863-79. Ó2017 AACR.

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“…174 Sándor et al showed that GDF-15 was responsible for fibroblast radioresistance, since silencing the gene rendered the cells more radiation-sensitive. 175 The same group investigated potential downstream targets of GDF-15 and showed that it could regulate some TP53 target genes such as TP53INP4, but it did not affect CDKN1A or GADD45A. Moreover, it was shown that one possible mechanism by which GDF-15 exerted its radioprotective effect is by abrogating the radiation induced early G2 block.…”

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confidence: 99%