Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation Potentially Involved in the Adaptive Response of Cancer Cells to Oxygen-Deficient Conditions

Abstract

The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed with the aryl hydrocarbon receptor nuclear translocator, bind to and activate target genes as enhancers of transcription. In addition to this common mechanism, the induction of the unfolded protein response and mTOR signaling in response to endoplasmic reticulum stress is also known to be involved in the adaptation to hypoxia conditions. Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition to the well-characterized stress response mechanisms described above, increasing experimental evidence suggests that Sp1 and HIFs collaborate to drive gene expression in cancer cells in response to hypoxia, thereby regulating additional adaptive responses to cellular oxygen deficiency. However, these characteristics of Sp1 and their biological merits have not been summarized. In this review, we will discuss the diverse mechanisms of transcriptional regulation by Sp1 and their potential involvement in the adaptive response of cancer cells to hypoxic tumor microenvironments.

Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy loss

“…We found p53 and SP1 might bind to DMR near CREB5 , which were validated by ChIP-qPCR. SP1 is a widely expressed transcription factor and plays critical roles in transcriptional regulation by binding to GC-rich cis-elements in many promoter regions [ 39 ]. SP1 can also interact with other transcription factors like methyl transferases, acetylases/de-acetylases, and other chromatin modifying molecules, which are involved in numerous cellular processes including cell growth, apoptosis, immune responses and so on [ 40 ].…”

Neem Leaf Glycoprotein Restrains VEGF Production by Direct Modulation of HIF1α-Linked Upstream and Downstream Cascades

“…Next, we look further into the binding capacity of HIF1α with other cofactors, like Sp1, CBP, p300, and we found that NLGP prevents colocalization of HIF1α with CBP, p300 and Sp1 but not with Sp3, which can competitively target HIF1α and Sp1 binding. Sp1 and Sp3 compete for binding to the HRE region as they share more than 90% sequence homology (39)(40)(41). Consequently, we observed significant less binding of active HIF1α complex with HRE region.…”

TLR-mediated miR-125b-5p downregulation enhances CD248-induced metastasis and drug resistance in colorectal cancer cells

“…However, the effect of miR-125b on drug resistance in colorectal cancer cells and the underlying mechanism by which miR-125b modulates CD248 expression still need to be investigated. Specificity protein 1 (Sp1), a basic transcriptional regulator for numerous genes, is usually related to carcinogenesis [18,19]. Sp1 binding to the promoter region of the CD248 gene activates its expression under high cell density culture conditions [18,20].…”

“…Specificity protein 1 (Sp1), a basic transcriptional regulator for numerous genes, is usually related to carcinogenesis [18,19]. Sp1 binding to the promoter region of the CD248 gene activates its expression under high cell density culture conditions [18,20]. According to the results of a miRNA microarray using chemoresistant colon cancer cells and a search using the web-based miRNA prediction software TargetScan (http://www.targetscan.org/), we found that Sp1 could be a target gene of miR-125b-5p.…”

“…Posttranscriptional regulation of Sp1 may be expected to play a key role in the development and progression of cancer. Sp1 overexpression is associated with poor prognosis in various cancers and influences several oncogenes and tumor suppressor genes [18,19]. However, the role of Sp1 and its underlying mechanism in controlling the expression of Sp1 in colon cancer is not yet understood.…”