HOXA1 enhances the cell proliferation, invasion and metastasis of prostate cancer cells

Abstract

HOXA1, a member of the HOX gene family, has been implicated in tumor progression. However, the role of HOXA1 in prostate cancer is not well-established. In the present study, we found that HOXA1 was highly expressed in prostate cancer cells. We then repressed the expression of HOXA1 by short hairpin RNA (shRNA) to investigate the function of HOXA1 in prostate cancer cells. Our in vitro data showed that knockdown of HOXA1 attenuated the growth, invasion and migration of prostate cancer DU-145 and PC-3 cells. Furthermore, knockdown of HOXA1 resulted in an increased E-cadherin level and decreased Snail and MMP-3 levels in the DU-145 cells. In addition, knockdown of HOXA1 inhibited activation of ERK1/2 and AKT in the DU-145 cells. Our in vivo data revealed that knockdown of HOXA1 suppressed the growth and metastasis of prostate cancer cells. Collectively, our findings suggest that HOXA1 is involved in the regulation of prostate cancer progression, including cell growth, migration, invasion and metastasis. Thus, downregulation of HOXA1 may be a novel approach for the treatment of prostate cancer.

The posterior HOXD locus: Its contribution to phenotype and malignancy of Ewing sarcoma

“…Several HOX genes were previously implicated in neoplastic transformation resulting in leukemia [23] as well as solid cancers derived from various organs [24,25]. Furthermore, the involvement of particular HOX genes such as HOXC13, HOXD3, HOXA1 in metastasis and invasiveness was recently demonstrated for melanoma, breast and prostate cancer, respectively [45][46][47].…”

HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-κB pathway in a transcription-independent manner

“…It also contributes to inner and middle ear development, basioccipital bone formation and patterning of the great arteries and outflow tract of the heart (4–6). Over the last two decades, HOXA1 has been linked to adult cancers in breast, lung, liver, prostate and the oral cavity, as well as to melanoma (7–12). In the context of breast cancer, HOXA1 has been identified as a mammary epithelial oncogene, where its forced expression is sufficient to induce the oncogenic transformation of immortalized human mammary epithelial cells to aggressive in vivo carcinoma (11,13).…”

HOX transcription factors and the prostate tumor microenvironment

“…In addition to the gelatinase class MMPs, the expression of two other MMPs, MMP-3 and MMP-14, is activated by HOX transcription factors [62,63] . MMP-14 differs from other MMPs as it is membrane bound through a transmembrane domain with its catalytic center on the outside of the cell [64] .…”

“…MMP-14 has been shown to be upregulated by HOXA3 expression [62] , and HOXA3 is overexpressed in a number of cancers, including prostate cancer [25] . Another HOX gene linked to the progression of prostate cancer is HOXA1, the expression of which promotes the proliferation, invasion and metastasis of prostate cancer cells [63] . A number of key downstream target genes of HOXA1 have been identified, including MMP-3, which has itself been linked to prostate tumor progression in a number of studies [68][69][70][71] , and polymorphisms in the MMP-3 gene have been identified as a risk factor for the development of prostate cancer [72] .…”

“…These include HOXA1, which inhibits the expression of E-cadherin [63] , a major component of the epithelial adherence junctions that mediate intercellular interactions [73] . The downregulation of E-cadherin expression is one of the changes that occurs during the epithelial to mesenchymal transition, the activation of which in cancer cells is a key step in tumor invasion and metastasis [74] .…”