HOXB5 induces invasion and migration through direct transcriptional up-regulation of β-catenin in human gastric carcinoma

Abstract

HOX (homeobox) genes encode a family of transcriptional regulators, which have an important role in morphogenesis and differentiation during embryonic development. Their deregulated expression is involved in the carcinogenesis of many human solid tumours. In the present study, we show that HOXB5 mRNA was significantly overexpressed in gastric cancer tissues compared with adjacent normal tissues. HOXB5-up-regulated cancer cells showed increased invasion and migration activity, but no change in proliferation activity, whereas HOXB5-down-regulated cells showed decreased invasion and migration activity. Up-regulation of HOXB5 resulted in up-regulation of β-catenin, whereas inhibition of HOXB5 expression by siRNA led to the down-regulation of β-catenin. Moreover, a significant correlation between HOXB5 and CTNNB1 (β-catenin) mRNA expression was detected in gastric cancer tissues. Furthermore, we found that HOXB5 binds directly to the CTNNB1 promoter region and activates the transcriptional expression of β-catenin, as well as its downstream target genes, encoding cyclin D1 and c-Myc, leading to an increase in the invasion and migration activity of human gastric cancer cells. Thus HOXB5 may be an important regulator of the Wnt/β-catenin signalling pathway, thereby contributing to gastric cancer progression and metastasis.

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

“…Multiple studies have highlighted the key role of the Wnt signaling pathway in carcinogenesis and neoplastic transformation of different forms of human cancer, including gastric cancer (48), colorectal cancer (45), breast cancer (19), and prostate cancer (17,22). HOX genes, including both HOXA13 and HOXB5, are able to participate in cancer development by activating the Wnt/␤-catenin signaling pathway (15,20). Interestingly enough, HOXB7 was identified as being an upregulated gene in CSCC based on the microarray data provided by the GSE66359 profile, which supported our hypothesis that HOXB7 might have participated in the regulation of CSCC.…”

MicroRNA-1275 suppresses cell growth, and retards G1/S transition in human nasopharyngeal carcinoma by down-regulation of HOXB5

“…Such as, HOXB5 is overexpressed in human gastric carcinoma and induces invasion and migration through direct transcriptional up-regulation of β-catenin (Hong et al 2015), and HOXB5 is aberrantly overexpressed in breast cancer tissues and cell lines and promotes proliferation and invasion of breast cancer cells (Lee et al 2015). Moreover, Luo et al reported that HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines and inhibition of HOXB5 suppressed the oncogenic function of cancer cells (Luo et al 2012).…”

“…We discover that HOXB5 is a direct target of miR-1275, and is up-regulated in several tumors, including gastric carcinoma (Hong et al 2015), breast cancer (Lee et al 2015), bladder cancer (Luo et al 2012), and oral squamous cell carcinoma (Tucci et al 2011). While whether HOXB5 is up-regulated in NPC is not be explored.…”

KLF8 Promotes Temozolomide Resistance in Glioma Cells via β-Catenin Activation

“…The Wnt/β-catenin signaling regulates cell viability, growth, apoptosis, and invasion in various types of cancer, including glioma [28][29][30], and inhibiting this pathway decreased viability and increased apoptosis of adrenocortical tumor cells [28]. Pharmacological or genetic inhibition of Wnt activity augmented the effects of alkylating drugs and restored chemosensitivity in different cancers.…”