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Background Past research has identified the family of Serum Amyloid A (SAA) proteins to be intricately involved in inflammatory signaling and various disease pathologies. In cancer patients, SAA proteins have been reported to be upregulated in blood and tumor tissue, correlating in many instances with disease progression. However, the exact role of SAA proteins in cancer pathology remains to be fully elucidated. We, therefore, investigated systemic SAA1 and SAA2 (SAA1/2) in modulating the inflammasome, cell cycle, apoptosis, and epithelial-to-mesenchymal transition (EMT). Methods Breast cancer allografts were established in wild-type mice (WT), and mice lacking the SAA1/2 orthologs (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with western blotting and H&E histological staining. Results WT tumor-bearing mice had increased levels of plasma SAA compared to WT control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of the systemic inflammatory markers, IL-1β, IL-6, and IL-10 compared to WT tumor-bearing mice. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from WT mice, decreased apoptotic (cytochrome c, caspases 9/3, PARP), and inflammasome (NFκB, caspase 1, NLRP3) signaling, with little to no tumor necrosis. Conclusions We show that systemic SAA1/2 promotes the activation of the NLRP3 inflammasome in breast cancer tumors and the generation of pro-inflammatory cytokines, which promotes apoptosis and tumor necrosis. Based on these findings, we hypothesize that SAA1/2-mediated necrosis is due to NLRP3-mediated pore formation in membranes, while apoptosis signaling is likely mediated via the TIF-IA-NF-κB-apoptosis axis.

Background: The availability of nutrients impacts cell size and growth rate in many organisms. Research in E. coli has traditionally focused on the influence of exogenous nutrient sources on cell size through their effect on growth and cell cycle progression. Utilising a set of mutants where three genes involved in glycogen degradation - glycogen phosphorylase (glgP), glycogen debranching enzyme (glgX) and maltodextrin phosphorylase (malP) - were disrupted, we examined if degradation of this energy storage compound affects cell size. Results: It was found that mutations to malP increased cell lengths and resulted in substantial heterogeneity of cell size. This was most apparent during exponential growth and the phenotype was unaccompanied by alterations in Z-ring occurrence, cellular FtsZ levels and generation times. ∆malP mutant cells did, however, show abnormal nuclear staining patterns and accumulate increased DnaA amounts at late growth stages, indicating a potential effect on DNA replication. Conclusion: This study reveals a link between glycogen metabolism and cell size in E. coli. A disrupted malP allele is associated with cell size heterogeneity and elongation at all stages of growth, without detectable changes to mass doubling time, FtsZ protein levels or division ring frequency.