title: Galectin-1 promotes lung cancer tumor metastasis by potentiating integrin α6β4 and Notch1/Jagged2 signaling pathway.
abstract: Lung cancer is a major cancer, leading in both incidence and mortality in the world, and metastasis underlies the majority of lung cancer-related deaths. Galectin-1, a glycan-binding protein, has been shown to be overexpressed in lung cancer and involved in tumor-mediated immune suppression. However, the functional role of galectin-1 in lung cancer per se remains unknown. We demonstrate that ectopic expression of galectin-1 in a low-metastatic CL1-0 lung cancer cell line promotes its migration, invasion and epithelial-mesenchymal transition. Conversely, we also show that suppression of galectin-1 expression in highly invasive CL1-5 and A549 cells inhibits migration and invasion of lung cancer cell and causes a mesenchymal-epithelial transition. These effects may be transduced by increasing the expression of integrin α6β4 and Notch1/Jagged2, which in turn co-operates in the phosphorylation of AKT. The effects of galectin-1 on cancer progression are reduced when integrin β4 and Notch1 are absent. Further study has indicated that galectin-1 knockdown prevents the spread of highly metastatic Lewis lung carcinoma in vivo. Our study suggests that galectin-1 represents a crucial regulator of lung cancer metastasis. Thus, the detection and targeted treatment of galectin-1-expressing cancer serves as a new therapeutic target for lung cancer.
authors: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Ya-Ling
authors: YL
authors: Hsu
authors: Cheng-Ying
authors: CY
authors: Wu
authors: Jen-Yu
authors: JY
authors: Hung
authors: Yi-Shiuan
authors: YS
authors: Lin
authors: Ming-Shyan
authors: MS
authors: Huang
authors: Po-Lin
authors: PL
authors: Kuo
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism*; D039663:Integrin beta4 / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072101:Jagged-2 Protein; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D037483:Galectin 1; D039161:Integrin alpha6beta4; D039663:Integrin beta4; D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; C445499:LGALS1 protein, human; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D051057:Proto-Oncogene Proteins c-akt