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Although the expression of p27 has been regarded as a prognostic parameter in human liver cancer since the implication of decreased p27 expression levels in the genesis and progression of hepatocellular carcinoma (HCC), the molecular mechanism linking p27 deficiency and HCC development is still unclear. Here, we report an increase in tumorigenesis and progression as well as an enhanced inflammatory response in p27 deficient mice (p27−/−) and hypothesize the possible mechanism. We show that p27−/− mice display increased proliferation and decreased apoptosis of tumor cells, accompanied by an increase in the serum inflammatory cytokines IL-6 and TNF-α. Furthermore, our data indicated that the increased number and signal transducers and activator of transcription 3 (STAT3) phosphorylation status of infiltrated inflammatory cells was accompanied by increased IL-6 and TNF-α mRNA levels in tumor and normal liver tissue in the p27−/− mice. Moreover, using tumor cell and splenocytes co-culture and tumor homologous transplantation, we validated our hypothesis in vitro and in vivo. Collectively, these data demonstrate that the loss of p27 promotes carcinogens-induced HCC genesis and progression via the elevation of inflammatory cytokines and the augmented activation of STAT3 signaling in tumor cells and infiltrated inflammatory cells. Altogether, the loss of the cyclin kinase inhibitor p27, traditionally regarded as a consequence of DNA damage, can in turn promote HCC progression through enhancing the inflammatory response, potentially representing a promising therapeutic target in the prevention of HCC genesis and progression. J. Cell. Physiol. 228: 1967-1976, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Phytoalexins play a crucial role in plant immunity. However, the mechanism of how phytoalexin is primed by beneficial microorganisms against broad‐spectrum pathogens remains elusive. This study showed that Bacillus cereus AR156 could trigger ISR against broad‐spectrum disease. RNA‐sequencing and camalexin content assays showed that AR156‐triggered ISR can prime the accumulation of camalexin synthesis and secretion‐related genes. Moreover, it was found that AR156‐triggered ISR elevates camalexin accumulation by increasing the expression of camalexin synthesis genes upon pathogen infection. We observed that the priming of camalexin accumulation by AR156 was abolished in cyp71a13 and pad3 mutants. Further investigations reveal that in the wrky33 mutant, the ability of AR156 to prime camalexin accumulation is abolished, and the mediated ISR against the three pathogens is significantly compromised. Furthermore, PEN3 and PDR12, acting as camalexin transporters, participate in AR156‐induced ISR against broad‐spectrum pathogens differently. In addition, salicylic acid and JA/ET signalling pathways participate in AR156‐primed camalexin synthesis to resist pathogens in different forms depending on the pathogen. In summary, B. cereus AR156 triggers ISR against Botrytis cinerea, Pst DC3000 and Phytophthora capsici by priming camalexin synthesis. Our study provides deeper insights into the significant role of camalexin for AR156‐induced ISR against broad‐spectrum pathogens. Summary statement: Beneficial rhizobacterium AR156 triggered ISR by enhancing camalexin accumulation in Arabidopsis, with WRKY33 acting as a positive regulator. PEN3 and PDR12 are involved in AR156‐induced ISR. Salicylic acid and JA/ET signalling pathways participate in AR156‐primed camalexin synthesis to resist various pathogens. [ABSTRACT FROM AUTHOR]