Anti-SETD7 monoclonal antibody, clone 3E21

RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RIOK1. FBXO6 specifically interacts with K411-methylated RIOK1 through its FBA domain to induce RIOK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. Functional experiments demonstrate the RIOK1 methylation reduces the tumor growth and metastasis in mice model. Importantly, the protein levels of CK2 and LSD1 show an inverse correlation with FBXO6 and SETD7 expression in human colorectal cancer tissues. Together, this study highlights the importance of a RIOK1 methylation-phosphorylation switch in determining colorectal and gastric cancer development.

Background In human breast, adipose tissue represents up to 80% of the total volume and plays a critical role in mammary gland remodeling. Given the emerging role of obesity in breast cancer growth and development, we explored the relationship between body mass index (BMI), as a proxy of woman's obesity status, and the expression in normal breast tissue from healthy women of a selected panel of genes, known to be involved in mammary gland homeostasis. Methods Two independent publicly available datasets, composed of 180 specimens of normal breast tissue from reduction mammoplasty were interrogated. Differential gene expression among BMI classes was evaluated by ANOVA, and partial correlation coefficient was used to assay the correlation between genes controlling for BMI. Results Despite the differences in microarray platforms and analytical procedures, the two datasets shared a core of 9 genes differentially expressed in BMI classes and significantly correlated with BMI. Four (44%) of these genes belong to the functional class of cytokines and cytokine receptors (IL1R1, IL2RA, IL12A, and IL12RB2). The others belong to the functional class of the epigenetic regulation (MEDAG and SETD7), signal transduction (STAT1), cell adhesion (ITGAV), and enzymatic activity (STS). Conclusions Although exploratory, present findings are in agreement with the role of inflammation modulators in the homeostasis of normal breast tissue and the believe that an increase in body adipose tissue may have a potentially dangerous local effect, through the increased expression of inflammation-related genes and the establishment of a low-grade chronic inflammation.