Abstract
This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC). The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways. HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G(0)-G(1) to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G(1)-S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity. Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies worldwide
HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P 1⁄4 0.012), distant metastasis (P 1⁄4 0.042), higher proliferation index (P 1⁄4 0.007) and poor survival of patients (P 1⁄4 0.005)
We showed that HOXB7 accelerated G0–G1 to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1
Summary
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Colorectal carcinogenesis is a multistep process involving progressive disruption of Authors' Affiliations: 1Department of Pathology, School of Basic Medical Sciences, Southern Medical University; 2Department of Pathology, Nanfang Hospital, Southern Medical University; 3Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou; and 4Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of ChinaNote: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).W.-T. Colorectal cancer (CRC) is one of the most common malignancies worldwide. Colorectal carcinogenesis is a multistep process involving progressive disruption of Authors' Affiliations: 1Department of Pathology, School of Basic Medical Sciences, Southern Medical University; 2Department of Pathology, Nanfang Hospital, Southern Medical University; 3Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou; and 4Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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