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Carcinogenesis explained within the context of a theory of organisms
mercredi 09 décembre 2020

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Descriptif

Exposé de Ana Soto (Tufts University School of Medicine, Dept Immunology ; Centre Cavaillès-République des savoirs, École Normale Supérieure, Paris)  dans le cadre du Séminaire Cavaillès (Histoire et Philosophie du vivant) organisé par la République des Savoirs à l'ENS-PSL.

Lacking an operational theory to explain the organization and behavior of matter in unicellular and multicellular organisms hinders progress in biology. Such a theory should address life cycles from ontogenesis to death. This theory would complement the theory of evolution that addresses phylogenesis and would posit theoretical extensions to accepted physical principles and default states in order to grasp the living state of matter and define proper biological observables (1).
The fundamental biological principles we proposed for the construction of a theory of organisms are: a) the default state (proliferation with variation and motility (2), b) the principle of organization which addresses the generation and maintenance of stability by closure of constraints, (3) and c) the principle of variation, which is generated both at the cellular and supracellular levels (4). Our experimental research and mathematical modeling efforts are guided by these principles.
For a century, the somatic mutation theory (SMT) has been the prevalent theory to explain carcinogenesis. According to the SMT, cancer is a cellular problem, and thus, the level of organization where it should be studied is the cellular level. Additionally, the SMT proposes that cancer is a problem of the control of cell proliferation and assumes that proliferative quiescence is the default state of cells in metazoa. In 1999, a competing theory, the tissue organization field theory (TOFT), was proposed. In contraposition to the SMT, the TOFT posits that cancer is a tissue-based disease whereby carcinogens (directly) and mutations in the germ-line (indirectly) alter the normal interactions between the diverse components of an organ, such as the stroma and its adjacent epithelium (5). The TOFT explicitly acknowledges that the default (unconstrained) state of all cells is proliferation with variation and motility. When taking into consideration the principle of organization, we posit that carcinogenesis can be explained as a relational problem whereby release of the constraints created by cell interactions and the physical forces generated by cellular agency lead cells within a tissue to regain their default state of proliferation with variation and motility. Within this perspective, what matters both in morphogenesis and carcinogenesis is not only molecules, but also biophysical forces generated by cells and tissues. Herein, we describe how the principles for a theory of organisms apply to the TOFT and thus to the study of carcinogenesis (6).

Literature cited
1.    Soto AM, Longo G, Miquel PA, Montévil M, Mossio M, Perret N, Pocheville A, Sonnenschein C. Toward a theory of organisms: Three founding principles in search of a useful integration. Prog Biophys Mol Biol. 2016 122:77-82.
2.    Soto AM, Longo G, Montévil M, Sonnenschein C. The biological default state of cell proliferation with variation and motility, a fundamental principle for a theory of organisms. Prog Biophys Mol Biol. 2016b Oct;122(1):16-23.
3.    Mossio M, Montévil M, Longo G. Theoretical principles for biology: Organization. Prog Biophys Mol Biol. 2016;122:24-35.


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Auteur(s)
Ana Soto
Tufts University
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Professeur en biologie cellulaire à la faculté de médecine de l’Université Tufts de Boston (USA).

Ana Soto a découvert que la lignée cellulaire de cancer du sein sur lequel elle travaillait depuis un certain temps proliférait de manière aberrante. Ele soumit son protocole de travail à une investigation digne d’un détective. En 1991, elle finit par mettre la main sur le coupable : la para-nonylphénol (un composé de la famille des alkylphénols), un « banal » additif aux plastiques, utilisé au laboratoire et ailleurs.

Ce composé agit en fait comme une hormone et stimule la croissance des cellules malignes et est en mesure de perturber tout l’équilibre hormonal.

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Dernière mise à jour : 12/07/2021