Use of Arabidopsis thaliana as a model to understand specific carcinogenic events: Comparison of the molecular machinery associated with cancer-hallmarks in plants and humans.

ABSTRACT

Model organisms are fundamental in cancer research given that they rise the possibility to characterize in a quantitative-objective fashion the organisms as a whole in ways that are infeasible in humans. From this perspective, model organisms with short generation times and established protocols for genetic manipulation allow the understanding of basic biology principles that might guide carcinogenic onset. The cancer-hallmarks (CHs) approach, a modular perspective for cancer understanding, stands that underlying the variability among different cancer types, critical events support the carcinogenic origin and progression. Thus, CHs as interconnected genetic circuitry, have a causal effect over cancer biogenesis and might represent a comparison scaffold among model organisms to identify and characterize evolutionarily conserved modules to understand cancer. Nevertheless, the identification of novel cancer regulators by comparative genomics approaches relies on selecting specific biological processes or related signaling cascades that limit the type of detected regulators, even more, holistic analysis from a systemic perspective is absent. Similarly, although the plant Arabidopsis thaliana has been used as a model organism to dissect specific disease-associated mechanisms, given the evolutionary distance between plants and humans, a general concern about the utility of using A. thaliana as a cancer model persists. In the present research, we take advantage of the CHs paradigm as a framework to establish a functional systemic comparison between plants and humans, that allowed the identification not only of specific novel key genetic regulators, but also, biological processes, metabolic systems, and genetic modules that might contribute to the neoplastic transformation. We propose five cancer-hallmarks that overlapped in conserved mechanisms and processes between Arabidopsis and human and thus, represent mechanisms which study can be prioritized in A. thaliana as an alternative model for cancer research. Additionally, derived from network analyses and machine learning strategies, a new set of potential candidate genes that might contribute to neoplastic transformation is described. These findings postulate A. thaliana as a suitable model to dissect, not all, but specific cancer properties, highlighting the importance of using alternative complementary models to understand carcinogenesis.