1. School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan;
2. Division of Pediatric Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan;
3. Department of Pathology, Cardinal Tien Hospital, New Taipei, Taiwan;
4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan;
5. Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei, Taiwan;
6. Department of Clinical and Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan;
7. NTU Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan;
8. Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan;
9. Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region. However, whether the HOXA5 could cooperate with p53 and contribute the inhibition of lung cancer cell invasion is still unclear. The aim of the current study is to elucidate the correlation of HOXA5 and p53 in tumor invasion and its prognostic influence in lung cancer patient specimens. Totally 71 cases of primary non-small cell lung cancer (NSCLC) were collected. The median follow-up period is 6.8 years. Immunohistochemical stain for p53 and HOXA5 were performed. Kaplan-Meier plot was done for overall survival analysis. In addition, lung cancer cell lines transfected with wild-type or mutated p53 constructs were overexpressed with HOXA5 for invasion assay. In human specimens, HOXA5 expressed mainly in the cytoplasm (54.1%) rather than nuclei (14.6%) of the NSCLC tumor part. The HOXA5 expression is higher in adenocarcinoma than in squamous cell carcinoma (P < 0.001). In addition, poor prognosis is seen in group with both non-immunoreactive for p53 and HOXA5. HOXA5 and p53 could cooperate to inhibit tumor cell invasion significantly partly by decreasing MMP2 activity in a concentration-dependent manner. Our studies provide new insights into how HOXA5 and p53 cooperate to contribute to the suppression of lung cancer cell invasion and play good prognostic roles in NSCLC.
Keywords: HOXA5, p53, invasion, prognosis, lung cancer.