The ELAVL3/MYCN positive feedback loop provides a therapeutic target for neuroendocrine prostate cancer

Neuroendocrine prostate cancer is a rapidly progressive and lethal disease characterized by early visceral metastasis, poor prognosis, and limited treatment options. Uncovering the oncogenic mechanisms could lead to the discovery of potential therapeutic avenues. Here, we demonstrate that the RNA-binding protein ELAVL3 is specifically upregulated in neuroendocrine prostate cancer and that overexpression of ELAVL3 alone is sufficient to induce the neuroendocrine phenotype in prostate adenocarcinoma. Mechanistically, ELAVL3 is transcriptionally regulated by MYCN and subsequently binds to and stabilizes MYCN and RICTOR mRNA. Moreover, ELAVL3 is shown to be released in extracellular vesicles and induce neuroendocrine differentiation of adenocarcinoma cells via an intercellular mechanism. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppresses tumor growth, reduces metastatic risk, and improves survival in neuroendocrine prostate cancer mouse models. Our results identify ELAVL3 as a critical regulator of neuroendocrine differentiation in prostate cancer and propose a drug repurposing strategy for targeted therapies.

 

Comments:

This is fascinating! It seems like the research findings highlight ELAVL3 as a pivotal player in the progression of neuroendocrine prostate cancer. Its role in inducing the neuroendocrine phenotype, along with its regulation by MYCN and its impact on stabilizing MYCN and RICTOR mRNA, sheds light on the mechanisms underlying this aggressive form of cancer.

The discovery that ELAVL3 can be released in extracellular vesicles, contributing to intercellular communication and promoting neuroendocrine differentiation in neighboring cells, is particularly intriguing. This suggests a potential avenue for understanding how this cancer type spreads and progresses.

The use of pyrvinium pamoate, an FDA-approved drug, to target ELAVL3 and subsequently suppress tumor growth, reduce metastatic risk, and improve survival in neuroendocrine prostate cancer mouse models is promising. Drug repurposing strategies like this can significantly accelerate the development of effective treatments, considering the urgency of addressing this aggressive and lethal disease.

This research paves the way for further investigations into ELAVL3 as a therapeutic target, offering hope for the development of more targeted and effective treatments for neuroendocrine prostate cancer.

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