title: HOXA5 inhibits metastasis via regulating cytoskeletal remodelling and associates with prolonged survival in non-small-cell lung carcinoma.
abstract: Homeobox genes comprise a family of regulatory genes that contain a common homeobox domain and act as transcription factors. Recent studies indicate that homeobox A5 (HOXA5) may serve as a tumour suppressor gene in breast cancers. However, the precise role and the underlying mechanism of HOXA5 in lung cancer remain unclear. Oligonucleotide microarrays and an invasion/metastasis lung adenocarcinoma cell line model were used to determine the correlation between HOXA5 expression and cancer cell invasion ability. We found that ectopic expression of HOXA5 in highly invasive cancer cells suppressed cell migration, invasion, and filopodia formation in vitro and inhibited metastatic potential in vivo. Knockdown of HOXA5 promoted the invasiveness of lung cancer cells. In addition, HOXA5 expression was associated with better clinical outcome in non-small cell lung cancer patients with wild-type EGFR. Furthermore, genome-wide transcriptomic and pathway analyses were performed to identify the potential molecular mechanisms. Our data showed that HOXA5 may bind to the promoters of the cytoskeleton-related genes and downregulate their mRNA and protein expression levels. Our studies provide new insights into how HOXA5 may contribute to the suppression of metastasis in lung cancer via cytoskeleton remodelling regulation. Therefore, targeted induction of HOXA5 may represent a promising approach for non-small-cell lung cancer therapy.
authors: Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
authors: Chi-Chung
authors: CC
authors: Wang
authors: Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan; NTU Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Kang-Yi
authors: KY
authors: Su
authors: NTU Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors: Hsuan-Yu
authors: HY
authors: Chen
authors: Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: So-Yi
authors: SY
authors: Chang
authors: Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
authors: Chi-Fan
authors: CF
authors: Shen
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors: Chia-Hung
authors: CH
authors: Hsieh
authors: Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Qi-Sheng
authors: QS
authors: Hong
authors: Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Ching-Cheng
authors: CC
authors: Chiang
authors: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Gee-Chen
authors: GC
authors: Chang
authors: Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan; NTU Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Pathology and Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan; Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Sung-Liang
authors: SL
authors: Yu
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors: Jeremy J W
authors: JJ
authors: Chen
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism*; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors