Transcription Factor ZBP-89 Drives a Feedforward Loop of β-Catenin Expression in Colorectal Cancer

Essien, Bryan E.; Sundaresan, Sinju; Ocadiz-Ruiz, Ramon; Chavis, Aaron; Tsao, Amy C.; Tessier, Arthur J.; Hayes, Michael M.; Photenhauer, Amanda; Saqui‐Salces, Milena; Kang, Anthony J.; Shah, Yatrik M.; Győrffy, Balázs; Merchant, Juanita L.

doi:10.1158/0008-5472.can-15-3150

Cited by 23 publications

(29 citation statements)

References 41 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the highest expression of STRAP in stage I may be involved in tumor progression. A similar expression pattern has been observed for another protein ZBP-89 that plays an important role in CRC progression and maintenance of cancer cell stemness (41). Together, high expression of STRAP in different stages of CRC may be linked to tumor progression and stemness phenotype.…”

Section: Discussionsupporting

confidence: 73%

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

Lin

Yuan

et al. 2017

Cancer Research

View full text Add to dashboard Cite

NOTCH signaling exerts essential roles in normal and malignant intestinal physiology and the homeostasis of cancer stem-like cells (CSC), but the basis for this latter role remains obscure. The signaling scaffold protein STRAP is upregulated in several cancers where it promotes tumorigenicity and metastasis. Here we report a novel oncogenic function for STRAP in maintaining CSC subpopulations in a heterogeneous mixture by antagonizing formation of the chromatin modifier PRC2 and by epigenetically activating NOTCH signals in human colorectal cancer (CRC). Silencing STRAP sensitized CRC cells to chemotherapeutic drugs in vitro and in vivo. STRAP depletion also contributed to a reduced stem-like phenotype of CRC cells, as indicated by reduced expression of the CSC signature and NOTCH signaling regulators in vitro and by diminished tumorigenesis in vivo. Genes encoding some upstream activators of NOTCH were highly enriched for H3K27me3, which form repressive chromatin domains upon STRAP silencing. Mechanistically, STRAP competitively disrupted association of the PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly. Restoring the NOTCH pathway by lentiviral expression of NICD1 or HES1 in STRAP-depleted tumor cells reversed the CSC phenotype. In 90 CRC clinical specimens, a significant positive correlation was documented between the expression of STRAP and HES1. Overall, our findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in CRC, with potential implications to improve treatment of this disease.

show abstract

Section: Discussionsupporting

confidence: 73%

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

Lin

Yuan

et al. 2017

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Through RNA pulldown and mass spectrometry analyses, ANXA2 was found to bind with lncRNA-MUF, and the binding led to upregulated b-catenin and the EMT process. Upregulation of b-catenin occurs in several cancers such as colorectal cancer (41), breast cancer (42), and liver cancer (43). Canonical Wnt signaling depends on b-catenin/ GSK-3b complex conformation and phosphorylation by GSK-3b, leading to b-catenin degradation (44,45).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA–MUF Interaction with ANXA2 and miR-34a

et al. 2017

View full text Add to dashboard Cite

Accumulating evidence suggests that cancer-associated mesenchymal stem cells (MSC) contribute to the development and metastasis of hepatocellular carcinoma (HCC). Aberrant expression of long noncoding RNAs (lncRNA) has been associated with these processes but cellular mechanisms are obscure. In this study, we report that HCC-associated mesenchymal stem cells (HCC-MSC) promote epithelial-mesenchymal transition (EMT) and liver tumorigenesis. We identified a novel lncRNA that we termed (MSC-upregulated factor) that is highly expressed in HCC tissues and correlated with poor prognosis. Depleting in HCC cells repressed EMT and inhibited their tumorigenic potential. Conversely, lncRNA-MUF overexpression accelerated EMT and malignant capacity. Mechanistic investigations showed that bound Annexin A2 (ANXA2) and activated Wnt/β-catenin signaling and EMT. Furthermore, lncRNA-MUF acted as a competing endogenous RNA for miR-34a, leading to Snail1 upregulation and EMT activation. Collectively, our findings establish a lncRNA-mediated process in MSC that facilitates hepatocarcinogenesis, with potential implications for therapeutic targeting..

show abstract

“…Furthermore, the induction of ZBP89 contributes to sustaining β -catenin levels, further promoting cancer cell proliferation. 95 …”

Section: Role Of Znfs In Diseasesmentioning

confidence: 99%

Zinc-finger proteins in health and disease

et al. 2017

View full text Add to dashboard Cite

Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes. The aim of this review is to provide a comprehensive summary of the current state of knowledge of this class of proteins. Firstly, we describe the actual classification of ZNFs, their structure and functions. Secondly, we focus on the biological role of ZNFs in the development of organisms under normal physiological and pathological conditions.

show abstract

Transcription Factor ZBP-89 Drives a Feedforward Loop of β-Catenin Expression in Colorectal Cancer

Cited by 23 publications

References 41 publications

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA–MUF Interaction with ANXA2 and miR-34a

Zinc-finger proteins in health and disease

Contact Info

Product

Resources

About