Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-κB in inflammation and cancer. Although it seems to fulfill a distinctly tumor-promoting role in many types of cancer, NF-κB has a confounding role in certain tumors. Understanding the activity and function of NF-κB in the context of tumorigenesis is critical for its successful taming, an important challenge for modern cancer biology.

Inflammation meets cancer, with NF-κB as the matchmaker

Diverse bilaterian clades emerged apparently within a few million years during the early Cambrian, and various environmental, developmental, and ecological causes have been proposed to explain this abrupt appearance. A compilation of the patterns of fossil and molecular diversification, comparative developmental data, and information on ecological feeding strategies indicate that the major animal clades diverged many tens of millions of years before their first appearance in the fossil record, demonstrating a macroevolutionary lag between the establishment of their developmental toolkits during the Cryogenian [(850 to 635 million years ago (Ma)], and the later ecological success of metazoans during the Ediacaran (635 to 541 Ma) and Cambrian (541 to 488 Ma) periods. We argue that this diversification involved new forms of developmental regulation, as well as innovations in networks of ecological interaction within the context of permissive environmental circumstances.

https://science.sciencemag.org/content/sci/334/6059/1091.full.pdf

The Cambrian conundrum: Early divergence and later ecological success in the early history of animals

Completion of genome sequences for many organisms allows a reasonably complete definition of the complement of extracellular matrix (ECM) proteins. In mammals this “core matrisome” comprises 300 proteins. In addition there are large numbers of ECMmodifying enzymes, ECM-binding growth factors, and other ECM-associated proteins. These different categories of ECM and ECM-associated proteins cooperate to assemble and remodelextracellularmatricesandbindtocellsthroughECMreceptors.TogetherwithreceptorsforECM-boundgrowthfactors,theyprovidemultipleinputsintocellstocontrolsurvival, proliferation, differentiation, shape, polarity, and motilityof cells. The evolution of ECM proteins was key in the transition to multicellularity, the arrangement of cells into tissue layers, and the elaboration of novel structures during vertebrate evolution. This key role of ECM is reflectedinthediversityofECMproteinsandthemodulardomainstructuresofECMproteins both allow their multiple interactions and, during evolution, development of novel protein architectures.

/pdf/overview-of-the-matrisome-an-inventory-of-extracellular-5d35qluk3d.pdf

Overview of the Matrisome—An Inventory of Extracellular Matrix Constituents and Functions

An understanding of ctenophore biology is critical for reconstructing events that occurred early in animal evolution. Toward this goal, we have sequenced, assembled, and annotated the genome of the ctenophore Mnemiopsis leidyi. Our phylogenomic analyses of both amino acid positions and gene content suggest that ctenophores rather than sponges are the sister lineage to all other animals. Mnemiopsis lacks many of the genes found in bilaterian mesodermal cell types, suggesting that these cell types evolved independently. The set of neural genes in Mnemiopsis is similar to that of sponges, indicating that sponges may have lost a nervous system. These results present a newly supported view of early animal evolution that accounts for major losses and/or gains of sophisticated cell types, including nerve and muscle cells.

/pdf/the-genome-of-the-ctenophore-mnemiopsis-leidyi-and-its-42jjahfc5w.pdf

The Genome of the Ctenophore Mnemiopsis leidyi and Its Implications for Cell Type Evolution

T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors are the major end point mediators of Wnt/Wingless signaling throughout metazoans. TCF/LEFs are multifunctional proteins that use their sequence-specific DNA-binding and context-dependent interactions to specify which genes will be regulated by Wnts. Much of the work to define their actions has focused on their ability to repress target gene expression when Wnt signals are absent and to recruit β-catenin to target genes for activation when Wnts are present. Recent advances have highlighted how these on/off actions are regulated by Wnt signals and stabilized β-catenin. In contrast to invertebrates, which typically contain one TCF/LEF protein that can both activate and repress Wnt targets, gene duplication and isoform complexity of the family in vertebrates have led to specialization, in which individual TCF/LEF isoforms have distinct activities.

/pdf/tcf-lefs-and-wnt-signaling-in-the-nucleus-3k7ekkip1l.pdf

TCF/LEFs and Wnt Signaling in the Nucleus

Sponges are an ancient group of animals that diverged from other metazoans over 600 million years ago. Here we present the draft genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef, and show that it is remarkably similar to other animal genomes in content, structure and organization. Comparative analysis enabled by the sequencing of the sponge genome reveals genomic events linked to the origin and early evolution of animals, including the appearance, expansion and diversification of pan-metazoan transcription factor, signalling pathway and structural genes. This diverse ‘toolkit’ of genes correlates with critical aspects of all metazoan body plans, and comprises cell cycle control and growth, development, somatic- and germ-cell specification, cell adhesion, innate immunity and allorecognition. Notably, many of the genes associated with the emergence of animals are also implicated in cancer, which arises from defects in basic processes associated with metazoan multicellularity.

/pdf/the-amphimedon-queenslandica-genome-and-the-evolution-of-uefiz61n92.pdf

Shengqiang Q. Shu

Papers

The Amphimedon queenslandica genome and the evolution of animal complexity