ABSTRACT
Obesity increases the incidence, progression and mortality of breast cancer among postmenopausal females. This is partly due to excessive estrogen production in the adipose tissue of obese females. Aromatase is a key enzyme in estrogen biosynthesis. In the current study, the tensional forcetriggered inducibility of aromatase expression was observed to vary in ASCs isolated from different diseasefree individuals. In addition, this phenomenon was associated with the activation of the aromatase PII promoter and its DNA methylation load. These findings highlight the impact of tensional forces on estrogen biosynthesis in obese females.
Subject(s)
Adipose Tissue/enzymology , Aromatase/metabolism , DNA Methylation , Adipose Tissue/cytology , Aromatase/genetics , Azacitidine/analogs & derivatives , Azacitidine/pharmacology , Cell Culture Techniques , Cells, Cultured , CpG Islands , Decitabine , Enzyme Activation/drug effects , Female , Humans , Obesity/metabolism , Obesity/pathology , Promoter Regions, Genetic , RNA, Messenger/metabolismABSTRACT
Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.