Tumor suppressors: enhancers or suppressors of regeneration?

Abstract

SummaryTumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine.

A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors

“…Other Kazal-type serine protease inhibitors in mammals serve as biomarkers for various forms of cancer, but their exact functions are only now emerging (reviewed in (Fradet, 2009)). As aspects of limb regeneration share some similarity to cancer (for instance, activation of stem cells and dedifferentiation, cell proliferation, re-activation of developmental pathways, and the wound response) (reviewed in (Pomerantz and Blau, 2013)), links between the two processes warrant further investigation. Future work will be necessary to determine if connections exist between the roles of Kazal-type inhibitors in other organisms and the role of kazald1 in axolotl limb regeneration.…”

Regeneration Genetics

“…One possible explanation for these disparities is that regenerative capacity is an adaptive trait, but it might be less associated than other traits with overall reproductive fitness. For instance, rapid scarring mechanisms and custom regulation of tumor suppressor genes in certain tissues might contribute greatly to overall fitness, whereas optimized mechanisms for generating a tissue replicate might not (90). Interestingly, regenerative capacity changes during development and progression through life stages.…”

The tumor suppressor HHEX inhibits axon growth when prematurely expressed in developing central nervous system neurons

“…Tumor-suppressive factors that prevent aberrant proliferation in dividing cells may act to restrict axon growth in neurons, whereas factors with oncogenic properties may act to promote axon growth (Pomerantz and Blau, 2013). Supporting this concept, signaling pathways involved in cancer progression have been found to affect neurite outgrowth (Buchser et al, 2010), most notably the mTOR pathway (Park et al, 2008) and the oncogene MYC (Belin et al, 2015).…”