title: 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.
authors.affiliation: Research Center for Molecular Therapeutic to GI Tract, Institute for Biomedical Science, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea.
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Hong
authors.affiliation: Department of Surgery, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea.
authors.forename: Oh
authors.initials: O
authors.lastname: Jeong
authors.affiliation: Research Center for Molecular Therapeutic to GI Tract, Institute for Biomedical Science, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Zhengri
authors.initials: Z
authors.lastname: Piao
authors.affiliation: Research Center for Molecular Therapeutic to GI Tract, Institute for Biomedical Science, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea.
authors.forename: Chen
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Surgery, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea.
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Jung
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Choi
authors.affiliation: Research Center for Molecular Therapeutic to GI Tract, Institute for Biomedical Science, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea Department of Surgery, Chonnam National University Hwasun Hospital, Jeonnam 519-763, Republic of Korea Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju 501-746, Republic of Korea parkyk@jnu.ac.kr.
authors.forename: Young-Kyu
authors.initials: YK
authors.lastname: Park
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C489126:HOXB5 protein, human; D018398:Homeodomain Proteins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D019938:Cyclin D1
keywords: HOXB5; gastric cancer; invasion; migration; β-catenin