RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

Abstract

Background Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial–mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. Methods We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. Results We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. Conclusions Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.

A Metastasis-Related lncRNA Signature Correlates With the Prognosis in Clear Cell Renal Cell Carcinoma

“…ERBB is a tyrosine kinase type receptor. When ERBB binds to its ligand, it will be phosphorylated to activate the downstream signaling pathway, affecting the occurrence and progression of tumor ( 27 ). MAPK pathway is key signaling pathway that conducts extracellular signal through tertiary kinase cascade and regulates many physiological processes, such as cell growth, apoptosis and death.…”

Regulation of Hedgehog Signaling by miRNAs and Nanoformulations: A Possible Therapeutic Solution for Colorectal Cancer

“…The binding of hyaluronic acid with CD44 results in the activation of epidermal growth factor receptor family kinases such as the MAPK and PI3/AkT that in turn promotes growth and proliferation in various cancers (138). Majority of CSCs population have CD44 surface markers along with other cell surface markers that increase invasiveness and stemness (139). Considering its abundance in CRC tumorous stem cells it has been reported as putative marker for the detection of invasiveness and metastasis.…”

Role of RUNX2 in Melanoma: A New Player in Tumor Progression and Resistance to Therapy

“…It has been found that RUNX2 promoted cell proliferation and invasion of colon cancer cells via estrogen/ERbeta pathway [10]. More recently, it has been demonstrated that RUNX2 could interact with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells [22]. It has been also recently reported that Integrative multi-omics analysis of a colon cancer cells with heterogeneous Wnt activity reveals RUNX2 as an epigenetic regulator of Epithelial-mesenchymal transition (EMT), the critical process which promotes cancer metastasis, stemness and resistance to treatment [23].…”