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A Systems-Based Key Innovation-Driven Approach Infers Co-option of Jaw Developmental Programs During Cancer Progression.

ABSTRACT: Cancer acquires metastatic potential and evolves via co-opting gene regulatory networks (GRN) of embryonic development and tissue homeostasis. Such GRNs are encoded in the genome and frequently conserved among species. Considering that all metazoa have evolved from a common ancestor via major macroevolutionary events which shaped those GRNs and increased morphogenetic complexity, we sought to examine whether there are any key innovations that may be consistently and deterministically linked with metastatic potential across the metazoa clades. To address tumor evolution relative to organismal evolution, we revisited and retrospectively juxtaposed seminal laboratory and field cancer studies across taxa that lie on the evolutionary lineage from cnidaria to humans. We subsequently applied bioinformatics to integrate species-specific cancer phenotypes, multiomics data from up to 42 human cancer types, developmental phenotypes of knockout mice, and molecular phylogenetics. We found that the phenotypic manifestations of metastasis appear to coincide with agnatha-to-gnathostome transition. Genes indispensable for jaw development, a key innovation of gnathostomes, undergo mutations or methylation alterations, are aberrantly transcribed during tumor progression and are causatively associated with invasion and metastasis. There is a preference for deregulation of gnathostome-specific versus pre-gnathostome genes occupying hubs of the jaw development network. According to these data, we propose our systems-based model as an in silico tool the prediction of likely tumor evolutionary trajectories and therapeutic targets for metastasis prevention, on the rationale that the same genes which are essential for key innovations that catalyzed vertebrate evolution, such as jaws, are also important for tumor evolution.

SUBMITTER: Marquardt S

PROVIDER: S-EPMC8207138 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Highlights • The OIS concept can be used to analyse multi-actor co-innovation partnerships.• Co-innovation partnerships in agriculture and forestry occur in many forms.• Often based on existing networks, they mobilise complementary forms of knowledge.• ‘Outreach’ practices to foster dialogue with a ‘larger periphery’ are commonly used.• The ‘enabling environment’ affects the performance of the co-innovation partnership. Innovation rests not only on discovery but also on cooperation and interactive learning. In agriculture, forestry and related sectors, multi-actor partnerships for ‘co-innovation’ occur in many forms, from international projects to informal ‘actor configurations’. Common attributes are that they include actors with ‘complementary forms of knowledge’ who collaborate in an innovation process, engage with a ‘larger periphery’ of stakeholders in the Agricultural Knowledge and Innovation System (AKIS) and are shaped by institutions. Using desk research and interviews, we reviewed, according to the Organisational Innovation Systems framework, the performance of 200 co-innovation partnerships from across Europe, selected for their involvement of various actors ‘all along the process’. Many of the reviewed partnerships were composed of actors that had previously worked together and most interviewees believed that no relevant actors had been excluded. In almost all cases, project targets and objectives were co-designed to a great or some extent, and the mechanisms applied to foster knowledge sharing between partners were considered to be very effective. Great importance was attached to communication beyond the partnership, not simply for dissemination but also for dialogue, and most interviewees evaluated the communication/outreach performance of their partnership very highly. Most partnerships received external funding, most did not use innovation brokers during the proposal writing process and two thirds had access to information they needed. We discuss the implications of these findings and question whether the AKIS concept as currently interpreted by many policy makers can adequately account for the regional differences encountered by co-innovation partnerships across Europe.

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A Systems-Based Key Innovation-Driven Approach Infers Co-option of Jaw Developmental Programs During Cancer Progression.

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