Chun-I Wang1, Chia-Jung Yu2,3,4, Yenlin Huang5, Jui-Shan Yi1,3, Hsing-Wen Cheng1, Huang-Kai Kao6,7, William Wei-Kai Lao6, Kai-Ping Chang1,3,7. 1. Department of Otolaryngology - Head and Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. 2. Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. 3. Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan. 4. Department of Thoracic Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. 5. Department of Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. 6. Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. 7. College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Abstract
BACKGROUND: The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression. METHODS: The KPNA2 expressions were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2-knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real-time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor-kappa B (NF-κB). RESULTS: The KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease-specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)-1β-induced nuclear import of NF-κB and MMP (MMP-1, MMP-3, and MMP-9) transcription. CONCLUSION: The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP-mediated metastasis.
BACKGROUND: The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression. METHODS: The KPNA2 expressions were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2-knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real-time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor-kappa B (NF-κB). RESULTS: The KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease-specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)-1β-induced nuclear import of NF-κB and MMP (MMP-1, MMP-3, and MMP-9) transcription. CONCLUSION: The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP-mediated metastasis.