1 Sep 2013

Are hallmarks of cancer related to evolutionary transitions?

Posted by jofr

Signal_transduction_pathways_svgBuddhini Samarasinghe started recently a series of blog posts to explain the hallmarks of cancer, the six essential biological capabilities acquired during the multistep development of human tumors. I wish there would be more people like her who are able to explain the complicated matter of molecular biology as simple and good as she does! It made me think if there is possibly a relation between the hallmarks of cancer and the major/minor evolutionary transitions on the way from primitive forms of early life to complex multicellular organisms.

In the last post we wrote about various forms of “cultural cancers” which appeared to be the well known *-isms we know from history, for instance nazism, fascism and communism. They seem to emerge through the merging of previously distinct systems. In biological organisms we have various various systems and sub-systems as well, namely a..

  • communication system (signaling)
  • circulatory system (supply and demand of nutrients)
  • immune system (defense and invasion)
  • metabolic system (consumption and production of energy)

They emerged during major and minor evolutionary transitions in the course of evolution. Evolutionary systems are best understood from a historical perspective. Could it be that the hallmarks of cancer are related to this evolutionary transitions? The larger the fallback, the more severe the disease? Then the most severe forms of cancer should be related to the oldest transitions, and the most “primitive systems”.

John Maynard Smith, Eörs Szathmáry, and Harold J. Morowitz wrote books to identify the major evolutionary transitions. Smith and Szathmáry defined 8 major transitions, Morowitz identified 28 transitions. 3-4 are related to the emergence of genes and self-replicating genetic information, the most import transitions from Morowitz here are number 10, 11 and 12:

  • Morowitz step 10: from prokaryotes to eukaryotes and cells with organelles
  • Morowitz step 11: from single celled life to multicelllularity
  • Morowitz step 12: cell-to-cell communication and cell signaling

and from Smith and Szathmáry number 4, 5 and 6:

  • Smith and Szathmáry step 4: from prokaryotes to eukaryotes
  • Smith and Szathmáry step 5: from asexual clones to sexual populations
  • Smith and Szathmáry step 6: from protists to multicellular organisms

If we try to associate the different transitions with the different hallmarks, we would arrive at the following connection:


Communication and Signal System

* Self-succiciency in growth signals, sustaining proliferative signaling
=> Morowitz step 12: cell-to-cell communication and cell signaling

* Evading growth suppressors (insensitivity to anti-growth signals)
=> Morowitz step 12: cell-to-cell communication and cell signaling

* Evading and resisting apoptosis (cell death)
=> Morowitz step 12: cell-to-cell communication and cell signaling
=> Morowitz step 11: multicelllularity


Immune System and Circulatory System

* Activating invasion and metastasis
=> Morowitz step 11: multicelllularity, immune system
(hijacking of immune system through cancer cells)

* Evading immune destruction (resistance immune system)
=> Morowitz step 11: multicelllularity, immune system
(resisting and hijacking of immune system)

* Inducing angiogenesis (blood vessel growth)
=> Morowitz step 11: multicelllularity, circulatory system


Metabolic and “Replicative” System

* Enabling replicative immortality (limitless replication, cell cycle regulation fail.)
=> Smith and Szathmáry: step 5 from asexual clones to sexual populations

* Reprogramming of energy metabolism (Mitochondria dependent metabolism)
=> Smith and Szathmáry: step 4 from prokaryotes to eukaryotes
=> Morowitz step 10: from prokaryotes to eukaryotes and cells with organelles

If we order the hallmarks in this way, then the worst and most aggresive cancers with the lowest survival rate should be associated with the oldest steps concerning energy metabolism and replicative immortality. And in fact in pancreatic cancer we can find proto-oncogenes like K-RAS which affect the cell cycle regulation  and the metabolic (!) pathway. In less aggresive cancers with higher survival rates such as breast cancer we should not find genes directly related to the oldest transitions, if this hypothesis is correct. Typical for breast cancer is in fact a mutation in the BRCA1 DNA repair gene.

So what do you think, does it make sense to say that the hallmarks of cancer are somehow related to evolutionary transitions? Or are they just evolutionary adaptations of evolving cells in a tumor to the ecosystem of the tumor itself? In any case it is important to investigate cancer and cancer genomes from an evolutionary perspective.

References

  • Harold J. Morowitz, “The Emergence of Everything – How the World Became Complex”, Oxford University Press, 2002
  • Richard E. Michod, “Darwinian Dynamics: Evolutionary Transitions in Fitness and Individuality”, Princeton University Press, 1999
  • John Maynard Smith and Eörs Szathmary, “The Major Transitions in Evolution”, Oxford University Press, 1997

(The picture is from Wikipedia shows the major signal transduction pathways)

 

Leave a Reply

Message: