https://scholars.lib.ntu.edu.tw/handle/123456789/502883
標題: | Galectin-1 promotes lung cancer progression and chemoresistance by upregulating p38 MAPK, ERK, and cyclooxygenase-2 | 作者: | Chung L.-Y. Tang S.-J. Sun G.-H. Chou T.-Y. Yeh T.-S. SUNG-LIANG YU Sun K.-H. |
公開日期: | 2012 | 卷: | 18 | 期: | 15 | 起(迄)頁: | 4037-4047 | 來源出版物: | Clinical Cancer Research | 摘要: | Purpose: This study is aimed at investigating the role and novel molecular mechanisms of galectin-1 in lung cancer progression. Experimental Design: The role of galectin-1 in lung cancer progression was evaluated both in vitro and in vivo by short hairpinRNA(shRNA)-mediated knockdown of galectin-1 in lung adenocarcinoma cell lines. To explore novel molecular mechanisms underlying galectin-1-mediated tumor progression, we analyzed gene expression profiles and signaling pathways using reverse transcription PCR and Western blotting. A tissue microarray containing samples from patients with lung cancer was used to examine the expression of galectin-1 in lung cancer. Results: We found overexpression of galectin-1 in non-small cell lung cancer (NSCLC) cell lines. Suppression of endogenous galectin-1 in lung adenocarcinoma resulted in reduction of the cell migration, invasion, and anchorage-independent growth in vitro and tumor growth in mice. In particular, COX-2 was downregulated in galectin-1-knockdown cells. The decreased tumor invasion and anchorage-independent growth abilities were rescued after reexpression of COX-2 in galectin-1-knockdown cells. Furthermore, we found that TGF-β1 promoted COX-2 expression through galectin-1 interaction with Ras and subsequent activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-κB pathway. Galectin-1 knockdown sensitized lung cancer cells to platinum-based chemotherapy (cisplatin). In addition, galectin-1 and COX-2 expression was correlated with the progression of lung adenocarcinoma, and high clinical relevance of both proteins was evidenced (n = 47). Conclusions: p38 MAPK, ERK, and COX-2 activation are novel mediators for the galectin-1-promoted tumor progression and chemoresistance in lung cancer. Galectin-1 may be an innovative target for combined modality therapy for lung cancer. ?2012 American Association for Cancer Research. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502883 | ISSN: | 1078-0432 | DOI: | 10.1158/1078-0432.CCR-11-3348 | SDG/關鍵字: | cisplatin; cyclooxygenase 2; galectin 1; immunoglobulin enhancer binding protein; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase p38; Ras protein; short hairpin RNA; transforming growth factor beta1; anchorage independent growth; animal cell; animal experiment; animal model; animal tissue; article; cancer growth; cancer invasion; cancer resistance; carcinoma cell; cell invasion; controlled study; disease association; down regulation; drug sensitization; enzyme activation; enzyme induction; gene expression profiling; gene overexpression; gene silencing; human; human cell; human tissue; in vitro study; in vivo study; lung adenocarcinoma; lung non small cell cancer; male; migration inhibition; molecular dynamics; mouse; nonhuman; priority journal; protein expression; protein function; protein protein interaction; reverse transcription polymerase chain reaction; signal transduction; tissue microarray; transcription initiation; tumor promotion; Western blotting; Adenocarcinoma; Animals; Antineoplastic Agents; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cisplatin; Cyclooxygenase 2; Disease Progression; Drug Resistance, Neoplasm; Galectin 1; HEK293 Cells; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; p38 Mitogen-Activated Protein Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transforming Growth Factor beta1; Up-Regulation |
顯示於: | 醫學檢驗暨生物技術學系 |
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