Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway

Abstract

Metastatic cutaneous squamous cell carcinoma (CSCC) is a major cause of death associated with non-melanoma skin cancer. The involvement of homeobox B7 (HOXB7) in cancers has been reported. Thus, the current study intends to explore the effect of HOXB7 on CSCC and its relationship with the Wnt/β-catenin signaling pathway. Initially, microarray-based gene expression profiling of CSCC was performed and HOXB7 was identified as an upregulated gene based on the microarray data of GSE2068. Following this, the experimental results indicated that HOXB7 and β-catenin formed a composite, demonstrating that endogenous HOXB7 binds to β-catenin. Subsequently, CSCC cells were treated with siRNA against HOXB7 or inhibitor of Wnt/β-catenin signaling pathway (IWR-1) in order to analyze any underlying regulatory mechanism of HOXB7 on the CSCC cells. Tumor growth involving xenografts in nude mice was also observed so as to explore whether or not HOXB7 could regulate subcutaneous tumor growth through in vivo culturing. In order to investigate the potential effects of HOXB7 on the Wnt/β-catenin signaling pathway, we determined the expression of HOXB7 and downstream genes of the Wnt/β-catenin signaling pathway. Notably, siRNA-mediated knockdown of HOXB7 inhibited the activation of the Wnt/β-catenin signaling pathway, thereby impeding the progression of cell viability, migration, and invasion as well as of the tumor growth, while contrarily facilitating cell apoptosis. Taken together, silencing of the HOXB7 has the mechanism of inactivating the Wnt/β-catenin signaling pathway, thereby accelerating cell apoptosis and suppressing cell migration and invasion in CSCC, which could provide a candidate target for the CSCC treatment.

HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

“…Studies on human non-small cell lung cancer (NSCLC) have shown that knocking down HOXB5 significantly inhibited cell proliferation by inhibiting β-catenin and the downstream targets c-Myc and cyclin D1 47 . In the cutaneous squamous cell carcinoma (CSCC) cells, HOXB7 bound to β-catenin, and HOXB7 knockdown reduced cell viability and tumor growth by inhibiting the Wnt/β-catenin signaling pathway 48 . HOXA9 transcriptional activation of WNT6 ultimately activated the canonical WNT/β-catenin pathway in glioblastoma (GBM) 49 .…”

Equine penile squamous cell carcinoma: expression of biomarker proteins and EcPV2

“…We discovered that a number of Wnt targets of transcriptions were upregulated in human penile squamous cell carcinomas, suggesting a role for this pathway in penile carcinoma 18 . Wnt as a core pathogenetic driver of squamous cell carcinoma in humans has also been observed in other tissues 50,51 . Additionally, aberrant expression of FRA1 through Wnt activation has also been shown in glioma cells, indicating a linkage 43 .…”

SFRP2 modulates non‑small cell lung cancer A549�cell apoptosis and metastasis by regulating mitochondrial fission via Wnt pathways

“…no. S7086; Selleck Chemicals) was added to the medium for 4 h, as previously described (26). To inhibit mitochondrial fission, cells were exposed to mitochondrial division inhibitor 1 (Mdivi1; 10 mM; Sigma-Aldrich; Merck KGaA) for 12 h at 37˚C after transduction of A549 cells with an SFRP2 overexpression vector (ad-SFrP2).…”