Targeting SP1 Transcription Factor in Prostate Cancer Therapy

Abstract

Transcription factors are proteins that regulate gene expression by binding to specific DNA sequences within gene promoter regions. Specificity protein (Sp) family transcription factors play a critical role in various cellular processes and have been shown to be associated with tumorigenesis. The Sp family consists of several members that contain a highly conserved DNA-binding domain composed of three zinc fingers at the C-terminus and serine/threonine- and glutamine-rich transactivation domains at the N-terminal. Sp1 is elevated in several cancers including prostate and is associated with the prognosis of patients. Sp1, Sp3, and Sp4 regulate a variety of cancer associated genes that are involved in cell cycle, proliferation, cell differentiation, and apoptosis. Studies have shown that in prostate cancer, Sp1 regulates important genes like androgen receptor, TGF-β, c-Met, fatty acid synthase, matrix metalloprotein (MT1-MMP), PSA, and α-integrin. These results highlight the importance of Sp1 in prostate cancer and emphasize the potential therapeutic value of targeting Sp1. Several strategies, including the use of natural and synthetic compounds, have been used to inhibit Sp1 in prostate cancer. These include polyphenol quercetin, betulinic acid, acetyl-11-keto-beta-boswellic acid, tea phenols, isothiocyanates, thiazolidinediones, arsenic trioxide, and selenium. This review will describe the association of Sp proteins in prostate cancer with a special emphasis on some of the agents tested to target Sp proteins for the treatment of this malignancy.

Casticin inhibits the activity of transcription factor Sp1 and the methylation of RECK in MGC803 gastric cancer cells

“…Sp1 promotes the expression of a number of molecules that positively regulate cell cycles and affects the methylation of the DNA CpG island (36). In numerous tumor tissues, Sp1 expression is high and its activity is positively correlated with the degree of tumor invasion, but negatively correlated with patient prognosis (37,38).…”

Membrane-type matrix metalloproteinases: expression, roles in metastatic prostate cancer progression and opportunities for drug targeting

“…Interestingly, both MT1-MMP and Sp1 levels were decreased in PC3 cells when PI3K and JNK were inhibited, and MT1-MMP levels were decreased in DU-145 cells when MEK was inhibited. These results suggest Sp1-mediated transcriptional regulation of MT1-MMP in prostate cancer cell lines via differential signalling control [13,37] . Sroka et al [25] additionally considered the relationship between IGF-1R and MT1-MMP in prostate cancer cells and tissues, the expression data for which were discussed earlier.…”

“…A study by Sankpal et al [37] provides evidence for regulation of MT1-MMP by specificity protein 1 (Sp1). Sp1 is expressed in a number of different cancers, and plays key regulatory roles in processes associated with prostate cancer progression and metastasis.…”

The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1

“…Numerous studies have reported interesting properties of the transcription factor, Sp1, which is overexpressed in various human tumors such as lung, prostate, pancreas, breast and colon cancer, among others (6). Sp1 has been implicated as a target for anti-cancer therapy.…”

“…Sp1 is highly expressed in tissues of prostate cancer, breast carcinomas, thyroid cancer, hepatocellular carcinomas, pancreatic cancer, colorectal cancer, gastric cancer and lung cancer when compared to normal tissues or cells (5,6). Previous studies showed that Sp1 plays an important role in carcinogenesis and metastasis of several human tumor types by regulating growth-related signal transduction, cell cycle control molecules, apoptosis, oncogenes, tumor suppressor genes, as well as angiogenesis-related factors (7,8).…”