The Downregulation of eIF3a Contributes to Vemurafenib Resistance in Melanoma by Activating ERK via PPP2R1B

The Downregulation of eIF3a Contributes to Vemurafenib Resistance in Melanoma by Activating ERK via PPP2R1B

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Vemurafenib, a BRAF V600E inhibitor, provides therapeutic transpharm online shopping benefits for patients with melanoma, but the frequent emergence of drug resistance remains a challenge.An understanding of the mechanisms underlying vemurafenib resistance may generate novel therapeutic strategies for patients with melanoma.Here, we showed that eIF3a, a translational regulatory protein, was an important mediator involved in vemurafenib resistance.eIF3a was expressed at significantly lower levels in vemurafenib-resistant A375 melanoma cells (A375R) than in parental A375 cells.

Overexpression of eIF3a enhanced the sensitivity to BRAF inhibitors by reducing p-ERK levels.Furthermore, eIF3a controlled ERK activity by regulating the expression of the phosphatase PPP2R1B via a translation mechanism, thus determining the sensitivity of melanoma cells to vemurafenib.In addition, a positive correlation between eIF3a and PPP2R1B expression was also observed in tumor samples from the Human Protein Atlas and TCGA databases.In conclusion, our studies reveal a previously unknown molecular mechanism depileve easy clean of BRAF inhibitor resistance, which may provide a new strategy for predicting vemurafenib responses in clinical treatment.