Nuclear Dishevelled targets gene regulatory regions and promotes tumor growth

다국어 초록 (Multilingual Abstract)

Dishevelled (DVL) critically regulates Wnt signaling and contributes to a wide spectrum of diseases and is important in normal and pathophysiological settings. However, how it mediates diverse cellular functions remains poorly understood. Recent discoveries have revealed that constitutive Wnt pathway activation contributes to breast cancer malignancy, but the mechanisms by which this occurs are unknown and very few studies have examined the nuclear role of DVL. Here, we have performed DVL3 ChIP‐seq analyses and identify novel target genes bound by DVL3. We show that DVL3 depletion alters KMT2D binding to novel targets and changes their epigenetic marks and mRNA levels. We further demonstrate that DVL3 inhibition leads to decreased tumor growth in two different breast cancer models in vivo. Our data uncover new DVL3 functions through its regulation of multiple genes involved in developmental biology, antigen presentation, metabolism, chromatin remodeling, and tumorigenesis. Overall, our study provides unique insight into the function of nuclear DVL, which helps to define its role in mediating aberrant Wnt signaling.













DVL3 target genes act in diverse processes such as regulation of immune responses, signal transduction and metabolism.

DVL3 binds to the histone methyltransferase KMT2D and co‐localizes with it to regulatory regions.

DVL3 depletion alters KMT2D binding to novel targets and the maintenance or deposition of H3K4me3 at these regions.

DVL3 depletion reduces tumor growth in vivo.


This study identifies novel gene targets of nuclear Dishevelled 3 and shows that DVL3 depletion decreases binding of the histone methyltransferase KMT2D, thereby altering epigenetic marks and mRNA levels of target genes and decreasing tumor growth.
This study identifies novel gene targets of nuclear Dishevelled 3 and shows that DVL3 depletion decreases binding of the histone methyltransferase KMT2D, thereby altering epigenetic marks and mRNA levels of target genes and decreasing tumor growth.