Rogue proliferation versus restorative protection: Where do we draw the line for Wnt and Forkhead signaling?

Abstract

Background: Disease entities such as diabetes, neurodegeneration and cardiovascular disorders affect a significant portion of the world's population. Objective: Given that cellular survival and longevity in multiple disorders are tied to oxidative stress, apoptotic cell injury and immune system deregulation, the development of robust therapeutic strategies rests heavily upon the ability to balance each of these parameters. Methods: Here we discuss two exciting signaling pathways, namely Wnt and mammalian forkhead transcription factors predominantly of the O class superfamily, which can share integrated cytoprotective pathways during oxidative stress but may also adversely influence cellular survival and promote cancer cell proliferation. Conclusion: Future investigations must elucidate the cellular determinants that govern the ability of Wnt and forkhead proteins to promote cellular longevity and possible disease remission but also allow for detrimental biological consequences and clinical compromise.

Keywords::

• apoptosis
• cancer
• cardiovascular
• diabetes
• forkhead
• Foxo
• immune system
• neurodegeneration
• oxidative stress
• stem cells
• wingless
• Wnt

Acknowledgments

We apologize to our colleagues whose work we were unable to cite as a result of article space limitations. This research was supported by the following grants (to Kenneth Maiese): American Diabetes Association, American Heart Association (National), Bugher Foundation Award, Janssen Neuroscience Award, LEARN Foundation Award, MI Life Sciences Challenge Award, Nelson Foundation Award, NIH NIEHS (P30 ES06639), and NIH NINDS/NIA.

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