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- W4361943399 abstract "<div>Abstract<p><b>Purpose:</b> Both phosphatidylinositol 3-kinase/AKT and RAS/mitogen-activated protein kinase signal transduction pathways mediate 4E-BP1 phosphorylation, releasing 4E-BP1 from the mRNA cap and permitting translation initiation. Given the prevalence of PTEN and BRAF mutations in melanoma, we first examined translation initiation, as measured by phosphorylated 4E-BP1 (p-4E-BP1), in metastatic melanoma tissues and cell lines. We then tested the association between amounts of total and p-4E-BP1 and patient survival.</p><p><b>Experimental Design:</b> Seven human metastatic melanoma cells lines and 72 metastatic melanoma patients with accessible metastatic tumor tissues and extended follow-up information were studied. Expression of 4E-BP1 transcript, total 4E-BP1 protein, and p-4E-BP1 was examined. The relationship between 4E-BP1 transcript and protein expression was assessed in a subset of patient tumors (<i>n</i> = 41). The association between total and p-4E-BP1 levels and survival was examined in the larger cohort of patients (<i>n</i> = 72).</p><p><b>Results:</b> 4E-BP1 was hyperphosphorylated in 4 of 7 melanoma cell lines harboring both BRAF and PTEN mutations compared with untransformed melanocytes or RAS/RAF/PTEN wild-type melanoma cells. 4E-BP1 transcript correlated with 4E-BP1 total protein levels as measured by the semiquantitative reverse-phase protein array (<i>P</i> = 0.012). High levels of p-4E-BP1 were associated with worse overall and post-recurrence survival (<i>P</i> = 0.02 and 0.0003, respectively).</p><p><b>Conclusion:</b> Our data show that translation initiation is a common event in human metastatic melanoma and correlates with worse prognosis. Therefore, effective inhibition of the pathways responsible for 4E-BP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients.</p></div>" @default.
- W4361943399 created "2023-04-05" @default.
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- W4361943399 date "2023-03-31" @default.
- W4361943399 modified "2023-10-14" @default.
- W4361943399 title "Data from Phosphorylated 4E-BP1 Is Associated with Poor Survival in Melanoma" @default.
- W4361943399 doi "https://doi.org/10.1158/1078-0432.c.6517965" @default.
- W4361943399 hasPublicationYear "2023" @default.
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