The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

ABSTRACT:The objective of the present study was to investigate how feeding a diet containing a type of purified starch entirely produced from normal or high amylose maize grains would affect rumen fermentation and blood profile in goats. Twenty rumen-cannulated growing goats were assigned equally to one of two dietary treatments according to a randomized controlled trial design and fed two total mixed rations with similar ingredients and chemical composition except for the types of purified maize starch. One type was the high amylose starch (HAS), and the other was the normal amylose starch (NAS). Compared to goats fed the NAS diet, goats fed the HAS diet had significantly higher ruminal pH (P = 0.00), molar proportions of acetate (P = 0.00), butyrate (P = 0.01) and isobutyrate (P = 0.00), acetate to propionate ratio (P = 0.00), plasma concentrations of glucose (P = 0.02) and C-reactive protein (P = 0.03), and plasma levels of insulin (P = 0.03) and gastrin (P = 0.04), but had significantly lower ruminal concentrations of lactate (P = 0.04) and total volatile fatty acids (P = 0.04), propionate molar percentage (P = 0.00), whole blood ammonia concentration (P = 0.02), plasma concentrations of urea nitrogen (P = 0.00) and creatinine (P = 0.02), plasma levels of glucagon (P = 0.02) and motilin (P = 0.04), and plasma activities of glutamic-oxaloacetic transaminase (P = 0.02) and creatine kinase (P = 0.03). In addition, the HAS diet in comparison to the NAS diet tended to raise whole blood hematocrit (P = 0.08), plasma concentrations of albumin (P = 0.09), branched-chain amino acids (P = 0.09), valine (P = 0.09), phenylalanine (P = 0.08) and proline (P = 0.07), plasma levels of growth hormone (P = 0.06) and interleukin-2 (P = 0.07), and plasma α-amylase (P = 0.05) activity in goats. In conclusion, results showed that feeding goats the HAS diet instead of the NAS diet had multiple beneficial effects.