I am interested in learning more about WNT signaling and regulation of WNT itself. All suggestions of references on this topic are very welcome!
Wnt pathway is largely classified into beta-catenin-dependent or -independent, also referred to as canonical pathway and non-canonical pathway. The former is minaly involved in the cellular proliferation via the transcriptional regulation of beta-catnin-itself, c-Myc, CyclinD1 etc. The latter is involved in the cellular polarity and migration potential.
I have done research on the relationship between redox stress and caonincal Wnt signal pathway in several cancer cells. ROS induces the intranuclear translocation of beta-catenin, thereby transiently activates the cellular survival and proliferation. It does not need to say that higher ROS than the threshold would induce cell-cycle arrest, senescence or apoptosis. Canonical Wnt pathway increases the transcriptional level of both CD44 (especially CD44 variant8-10, which erases ROS via CD44v8-10-xCT-GSH axis) and c-Myc, one of the most famous proto-oncogenes. Due to the the difference in the half-life period, ROS-induced canonical Wnt signal activation finally regulates the negative feedback machinery between ROS and c-Myc. Therefore we could observe both in vitro and invivo that c-Myc and CD44v8-10 tend to show the inversed expression pattern each other.
Ref.
Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation.
Yoshida GJ, Saya H.
Biochem Biophys Res Commun. 2014 Jan 10;443(2):622-7.
I would like to add some more information about the relationship of inflammation and beta-catenin-dependent Wnt signal pathway. The activity of canonical Wnt signal transduction in the SZ95 sebaceous gland immortalized cells have been revealed to be enhanced on exposure to PGE2. Other reports have also focused on how chronic inflammation due to excessive PGE2 production causes SPEM, the precursor lesion of gastric cancer.
Ref. Three-dimensional culture of sebaceous gland cells revealing the role of prostaglandin E2-induced activation of canonical Wnt signaling. Yoshida GJ, Saya H, Zouboulis CC.
Indra- I would start with thinking just about Wnt5a. There are several references as well as gene info in Bauer M. et al (2013) Wnt5a encodes two isoforms with distinct functions in cancer. PLoS ONE 8 (11): e80526. Also do a PubMed search on K. Leandersson. Not very much is underwood about transcriptional activation of different Wnt lignads.
Are you looking for embryonic development of stem cells, or cancer? or other? there is a lot of really good review papers out there
I am interested in the regulation of WNT proteins in the context of cancer. I have found a lot of information on WNT pathways and its target genes, but I don't seem to find a lot of information on how WNT gene expression and protein stability is regulated. Thank you Dr. Macleod for your answer, it seems to confirm my impression. Thanks everyone for the answers so far! I find this a very intriguing topic.
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