TAF4b and Jun/Activating Protein-1 Collaborate to Regulate the Expression of Integrin α6 and Cancer Cell Migration Properties

Abstract

The TAF4b subunit of the transcription factor IID, which has a central role in transcription by polymerase II, is involved in promoter recognition by selective recruitment of activators. The activating protein-1 (AP-1) family members participate in oncogenic transformation via gene regulation. Utilizing immunoprecipitation of endogenous protein complexes, we documented specific interactions between Jun family members and TATA box binding protein-associated factors (TAF) in colon HT29 adenocarcinoma cells. Particularly, TAF4b and c-Jun were found to colocalize and interact in the nucleus of advanced carcinoma cells and in cells with epithelial-tomesenchymal transition (EMT) characteristics. TAF4b was found to specifically regulate the AP-1 target gene involved in EMT integrin α6, thus altering related cellular properties such as migration potential. Using a chromatin immunoprecipitation approach in colon adenocarcinoma cell lines, we further identified a synergistic role for TAF4b and c-Jun and other AP-1 family members on the promoter of integrin α6, underlining the existence of a specific mechanism related to gene expression control. We show evidence for the first time of an interdependence of TAF4b and AP-1 family members in cell type-specific promoter recognition and initiation of transcription in the context of cancer progression and EMT. Mol Cancer Res; 8(4); 554-68. ©2010 AACR.

Overexpression of Thy1 and ITGA6 is associated with invasion, metastasis and poor prognosis in human gallbladder carcinoma

“…In addition, the dysregulation of ITGA6 can trigger a complex cascade of effects on the expression levels of other cell migration-related genes, including those coding for ECM and chemokine ligands and receptors. Although ITGA6 is involved in the invasion and metastasis of multiple tumors, its biological effects appear to be tissue type specific (18,19,33–36). The present study observed that ITGA6 expression was significantly increased in tumor tissue compared with non-tumor tissue.…”

Roles of STAT3 and ZEB1 Proteins in E-cadherin Down-regulation and Human Colorectal Cancer Epithelial-Mesenchymal Transition

“…The transforming growth factor-␤ (TGF-␤) signaling and activated Ras pathways have been implicated as key EMT inducers in CRC cancer (10 -11). The Wnt, PI3K/AKT, and other signaling pathways may also play an important role in the EMT process in CRC progression (12)(13)(14)(15). Recently, accumulating evidence has indicated that abnormalities in the Janus kinase/signal transducer and activator of transcription (JAK/ STAT) pathway are involved in CRC oncogenesis (16,17).…”

Structure, assembly and dynamics of macromolecular complexes by single particle cryo-electron microscopy

“…A large extend of regulation is performed at the transcriptional level when the information carried by specific DNA sequence (the genes) is transcribed into a messenger RNA molecule (mRNA) by the RNA polymerase II enzyme. Misregulated gene expression underlies many human pathologies, as indicated by germ-line and somatic mutations in transcription regulatory genes that lead to genetic disease [17-20], developmental syndromes[21], neurological diseases [22], epigenetic perturbations [23] and cancer [21,24]. Most intensively studied is the initiation step, which determines which genes are turned on to express a specific piece of genetic information in response to external signaling events.…”