Abstract
Stau1 is a pluripotent RNA-binding protein that is responsible for the post-transcriptional regulation of a multitude of transcripts. Here, we observed that lung cancer patients with a high Stau1 expression have a longer recurrence free survival. Strikingly, Stau1 did not impair cell proliferation in vitro, but rather cell migration and cell adhesion. In vivo, Stau1 depletion favored tumor progression and metastases development. In addition, Stau1 depletion strongly impaired vessel maturation. Among a panel of candidate genes, we specifically identified the mRNA encoding the cell adhesion molecule Thrombospondin 1 (THBS1) as a new target for Staufen-mediated mRNA decay. Altogether, our results suggest that regulation of THBS1 expression by Stau1 may be a key process involved in lung cancer progression.
Highlights
Given that RNA-binding proteins (RBPs) play a critical role in ensuring that proteins involved in the same biological pathway are translated in a highly coordinated fashion, it is perhaps no surprise that recent research has linked RBPs to the modulations of cell survival and homeostasis
We show that Stau1 expression is upregulated in non-small cell lung cancer and that high Stau1 expression is associated with better survival rate of patients with lung cancer
Using shRNA as a means to downregulate Stau1 expression in the H460 lung cancer cell line, we showed that Stau1 depletion enhances cell migration and invasiveness in vitro and facilitates tumor development and metastasis in mice
Summary
Given that RNA-binding proteins (RBPs) play a critical role in ensuring that proteins involved in the same biological pathway are translated in a highly coordinated fashion, it is perhaps no surprise that recent research has linked RBPs to the modulations of cell survival and homeostasis. Even a slight modulation in the expression/activity of a single RBP can deeply impact one or more pathway(s) by altering a large network of downstream regulated genes. Many RBPs have been identified as critical players in the different steps of cancer development and progression. Among these RBPs, Stau appears as a key component of cancer development, as there is increasing evidence establishing a correlation between the deregulation of its expression and tumor progression
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