GSK3β inactivation promotes the oncogenic functions of EZH2 and enhances methylation of H3K27 in human breast cancers.

During the process of tumorigenesis, inactivation of tumor suppressors is a critical step. EZH2, a histone methyltransferase, promotes cell growth and migration through catalyzing trimethylation of histone H3 at Lys 27 (H3K27me3) and plays an important role in tumorigenesis. Its expression can be controlled by phosphorylation.

AKT1 Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer through Phosphorylation-Dependent Twist1 Degradation.

Epithelial-to-mesenchymal transition (EMT) is an essential physiologic process that promotes cancer cell migration, invasion, and metastasis. Several lines of evidence from both cellular and genetic studies suggest that AKT1/PKBα, but not AKT2 or AKT3, serves as a negative regulator of EMT and breast cancer metastasis. However, the underlying mechanism by which AKT1 suppresses EMT remains poorly defined.

MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer.

Sirtuin 6 (SIRT6) is associated with longevity and is also a tumor suppressor. Identification of molecular regulators of SIRT6 might enable its activation therapeutically in cancer patients. In various breast cancer cell lines, we found that SIRT6 was phosphorylated at Ser(338) by the kinase AKT1, which induced the interaction and ubiquitination of SIRT6 by MDM2, targeting SIRT6 for protease-dependent degradation.

Mesenchymal CD44 expression contributes to the acquisition of an activated fibroblast phenotype via TWIST activation in the tumor microenvironment.

Tumor-stroma interactions play a crucial role in cancer progression by eliciting factors that promote proliferative, angiogenic, and invasive supports to the tumor microenvironment. Mesenchymal stromal/stem cells (MSC) contribute to stroma in part as cancer-associated fibroblasts (CAF), but a complete understanding of how MSC contribute to the tumor stroma is lacking. In this study, we show how CAF phenotypes rely upon MSC expression of the multifunctional cell surface glycoprotein CD44, a putative stem cell marker.

Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer.

With rapid development of sequencing technologies such as deep sequencing and whole genome high-density tiling array, we now know that most of the "junk" genomic sequences are transcribed as non-coding RNAs (ncRNAs). A large number of long ncRNA transcripts (> 200bp) have been identified, and these long ncRNAs (LncRNAs) are found to be crucial regulators for epigenetic modulation, transcription, and translation. In this review, we briefly summarize the regulatory function of LncRNAs with a particular focus on the underlying mechanisms of LncRNAs in oncogenesis, tumor metastasis and suppression.

The crosstalk of mTOR/S6K1 and Hedgehog pathways.

Esophageal adenocarcinoma (EAC) is the most prevalent esophageal cancer type in the United States. The TNF-α/mTOR pathway is known to mediate the development of EAC. Additionally, aberrant activation of Gli1, downstream effector of the Hedgehog (HH) pathway, has been observed in EAC.

Epithelial-mesenchymal transition induced by TNF-α requires NF-κB-mediated transcriptional upregulation of Twist1.

Proinflammatory cytokines produced in the tumor microenvironment facilitate tumor development and metastatic progression. In particular, TNF-α promotes cancer invasion and angiogenesis associated with epithelial-mesenchymal transition (EMT); however, the mechanisms underlying its induction of EMT in cancer cells remain unclear. Here we show that EMT and cancer stemness properties induced by chronic treatment with TNF-α are mediated by the upregulation of the transcriptional repressor Twist1.

Acetylation of EGF receptor contributes to tumor cell resistance to histone deacetylase inhibitors.

Alteration of epidermal growth factor receptor (EGFR) is involved in various human cancers and has been intensively investigated. A plethora of evidence demonstrates that posttranslational modifications of EGFR play a pivotal role in controlling its function and metabolism. Here, we show that EGFR can be acetylated by CREB binding protein (CBP) acetyltransferase.